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Conserved domains on  [gi|260654708|ref|NP_001159531|]
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hydroxymethylglutaryl-CoA lyase, mitochondrial isoform 2 precursor [Homo sapiens]

Protein Classification

beta/alpha barrel domain-containing protein( domain architecture ID 229392)

beta/alpha barrel domain-containing protein belongs to a large superfamily with a wide variety of enzymatic functions

Graphical summary

 Zoom to residue level

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List of domain hits

 Name Accession Description Interval E-value
TIM super family cl21457
TIM-like beta/alpha barrel domains; A large family of domains similar to triose phosphate ...
 17-254 1.54e-126

TIM-like beta/alpha barrel domains; A large family of domains similar to triose phosphate isomerase (TIM) which, in general, share an eight beta/alpha closed barrel structure.


The actual alignment was detected with superfamily member PLN02746:

Pssm-ID: 473867  Cd Length: 347  Bit Score: 362.57  E-value: 1.54e-126
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  17 SLRAVSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQ 96
Cdd:PLN02746  31 GVAHMHNKLLKGLPKFVKIVEVGPRDGLQNEKNIVPTSVKVELIQRLVSSGLPVVEATSFVSPKWVPQLADAKDVMAAVR 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  97 KFPGINYPVLTPNLKGFEAA------------------------------------------------------------ 116
Cdd:PLN02746 111 NLEGARFPVLTPNLKGFEAAiaagakevavfasasesfsksnincsieeslvryrevalaakkhsipvrgyvscvvgcpi 190

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 117 -----------VTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVV 185
Cdd:PLN02746 191 egpvppskvayVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALANILVSLQMGISTV 270

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 260654708 186 DSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL 254
Cdd:PLN02746 271 DSSVAGLGGCPYAKGASGNVATEDVVYMLNGLGVSTNVDLGKLMAAGDFISKHLGRPSGSKTAVALSAR 339
 
Name Accession Description Interval E-value
PLN02746 PLN02746
hydroxymethylglutaryl-CoA lyase
 17-254 1.54e-126

hydroxymethylglutaryl-CoA lyase


Pssm-ID: 178347  Cd Length: 347  Bit Score: 362.57  E-value: 1.54e-126
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  17 SLRAVSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQ 96
Cdd:PLN02746  31 GVAHMHNKLLKGLPKFVKIVEVGPRDGLQNEKNIVPTSVKVELIQRLVSSGLPVVEATSFVSPKWVPQLADAKDVMAAVR 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  97 KFPGINYPVLTPNLKGFEAA------------------------------------------------------------ 116
Cdd:PLN02746 111 NLEGARFPVLTPNLKGFEAAiaagakevavfasasesfsksnincsieeslvryrevalaakkhsipvrgyvscvvgcpi 190

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 117 -----------VTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVV 185
Cdd:PLN02746 191 egpvppskvayVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALANILVSLQMGISTV 270

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 260654708 186 DSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL 254
Cdd:PLN02746 271 DSSVAGLGGCPYAKGASGNVATEDVVYMLNGLGVSTNVDLGKLMAAGDFISKHLGRPSGSKTAVALSAR 339
DRE_TIM_HMGL cd07938
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; ...
 35-237 4.54e-126

3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; 3-hydroxy-3-methylglutaryl-CoA lyase (HMGL) catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, one of the terminal steps in ketone body generation and leucine degradation, and is a key enzyme in the pathway that supplies metabolic fuel to extrahepatic tissues. Mutations in HMGL cause a human autosomal recessive disorder called primary metabolic aciduria that affects ketogenesis and leucine catabolism and can be fatal due to an inability to tolerate hypoglycemia. HMGL has a TIM barrel domain with a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. The cleavage of HMG-CoA requires the presence of a divalent cation like Mg2+ or Mn2+, and the reaction is thought to involve general acid/base catalysis. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163676  Cd Length: 274  Bit Score: 358.63  E-value: 4.54e-126
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  35 IVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFE 114
Cdd:cd07938    1 IVEVGPRDGLQNEKTFIPTEDKIELIDALSAAGLRRIEVTSFVSPKWVPQMADAEEVLAGLPRRPGVRYSALVPNLRGAE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 115 AA-----------------------------------------------------------------------VTKKFYS 123
Cdd:cd07938   81 RAlaagvdevavfvsasetfsqknincsiaeslerfepvaelakaaglrvrgyvstafgcpyegevppervaeVAERLLD 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 124 MGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQGASG 203
Cdd:cd07938  161 LGCDEISLGDTIGVATPAQVRRLLEAVLERFPDEKLALHFHDTRGQALANILAALEAGVRRFDSSVGGLGGCPFAPGATG 240

                        250       260       270
                 ....*....|....*....|....*....|....
gi 260654708 204 NLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQ 237
Cdd:cd07938  241 NVATEDLVYMLEGMGIETGIDLDKLLAAARWISE 274
HMGL-like pfam00682
HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and ...
 32-235 1.44e-61

HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and a region of pyruvate carboxylase.


Pssm-ID: 459902 [Multi-domain]  Cd Length: 264  Bit Score: 194.48  E-value: 1.44e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708   32 RVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETtsfvspkWVPQMG-DHTEVLKGIQKFPGIN--YPVLTP 108
Cdd:pfam00682   1 AVAICDTTLRDGEQALGVAFSIDEKLAIARALDAAGVDEIEV-------GFPAASeDDFEVVRAIAKVIPHAriLVLCRA 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  109 NLKGFEAAV---------------------------------------------------------------------TK 119
Cdd:pfam00682  74 REHDIKAAVealkgagavrvhvfiatsdlhrkyklgkdreevakravaavkaarsrgidvefspedasrtdpeflaevVE 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  120 KFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVP-LAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGgcpya 198
Cdd:pfam00682 154 AAIEAGATRINIPDTVGVLTPNEAAELISALKARVPnKAIISVHCHNDLGMAVANSLAAVEAGADRVDGTVNGIG----- 228

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 260654708  199 qGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFI 235
Cdd:pfam00682 229 -ERAGNAALEEVAAALEGLGVDTGLDLQRLRSIANLV 264
LeuA COG0119
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; ...
 129-242 6.77e-17

Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; Isopropylmalate/homocitrate/citramalate synthases is part of the Pathway/BioSystem: Isoleucine, leucine, valine biosynthesis


Pssm-ID: 439889 [Multi-domain]  Cd Length: 452  Bit Score: 79.44  E-value: 6.77e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 129 ISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGG-CpyaqgasGNLAT 207
Cdd:COG0119  165 INLPDTVGGATPNEVADLIEELRERVPDVILSVHCHNDLGLAVANSLAAVEAGADQVEGTINGIGErA-------GNAAL 237

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 260654708 208 EDLV---YMLegLGIHTGVNLQKLLEAGNFICQALNRK 242
Cdd:COG0119  238 EEVVmnlKLK--YGVDTGIDLSKLTELSRLVSEITGLP 273
 
Name Accession Description Interval E-value
PLN02746 PLN02746
hydroxymethylglutaryl-CoA lyase
 17-254 1.54e-126

hydroxymethylglutaryl-CoA lyase


Pssm-ID: 178347  Cd Length: 347  Bit Score: 362.57  E-value: 1.54e-126
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  17 SLRAVSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQ 96
Cdd:PLN02746  31 GVAHMHNKLLKGLPKFVKIVEVGPRDGLQNEKNIVPTSVKVELIQRLVSSGLPVVEATSFVSPKWVPQLADAKDVMAAVR 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  97 KFPGINYPVLTPNLKGFEAA------------------------------------------------------------ 116
Cdd:PLN02746 111 NLEGARFPVLTPNLKGFEAAiaagakevavfasasesfsksnincsieeslvryrevalaakkhsipvrgyvscvvgcpi 190

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 117 -----------VTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVV 185
Cdd:PLN02746 191 egpvppskvayVAKELYDMGCYEISLGDTIGVGTPGTVVPMLEAVMAVVPVDKLAVHFHDTYGQALANILVSLQMGISTV 270

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 260654708 186 DSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTSSKVAQATCKL 254
Cdd:PLN02746 271 DSSVAGLGGCPYAKGASGNVATEDVVYMLNGLGVSTNVDLGKLMAAGDFISKHLGRPSGSKTAVALSAR 339
DRE_TIM_HMGL cd07938
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; ...
 35-237 4.54e-126

3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; 3-hydroxy-3-methylglutaryl-CoA lyase (HMGL) catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, one of the terminal steps in ketone body generation and leucine degradation, and is a key enzyme in the pathway that supplies metabolic fuel to extrahepatic tissues. Mutations in HMGL cause a human autosomal recessive disorder called primary metabolic aciduria that affects ketogenesis and leucine catabolism and can be fatal due to an inability to tolerate hypoglycemia. HMGL has a TIM barrel domain with a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. The cleavage of HMG-CoA requires the presence of a divalent cation like Mg2+ or Mn2+, and the reaction is thought to involve general acid/base catalysis. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163676  Cd Length: 274  Bit Score: 358.63  E-value: 4.54e-126
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  35 IVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFE 114
Cdd:cd07938    1 IVEVGPRDGLQNEKTFIPTEDKIELIDALSAAGLRRIEVTSFVSPKWVPQMADAEEVLAGLPRRPGVRYSALVPNLRGAE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 115 AA-----------------------------------------------------------------------VTKKFYS 123
Cdd:cd07938   81 RAlaagvdevavfvsasetfsqknincsiaeslerfepvaelakaaglrvrgyvstafgcpyegevppervaeVAERLLD 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 124 MGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPYAQGASG 203
Cdd:cd07938  161 LGCDEISLGDTIGVATPAQVRRLLEAVLERFPDEKLALHFHDTRGQALANILAALEAGVRRFDSSVGGLGGCPFAPGATG 240

                        250       260       270
                 ....*....|....*....|....*....|....
gi 260654708 204 NLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQ 237
Cdd:cd07938  241 NVATEDLVYMLEGMGIETGIDLDKLLAAARWISE 274
PRK05692 PRK05692
hydroxymethylglutaryl-CoA lyase; Provisional
 29-244 6.97e-121

hydroxymethylglutaryl-CoA lyase; Provisional


Pssm-ID: 180206  Cd Length: 287  Bit Score: 346.10  E-value: 6.97e-121
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  29 LPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTP 108
Cdd:PRK05692   1 LPKRVKIVEVGPRDGLQNEKRFIPTADKIALIDRLSAAGLSYIEVASFVSPKWVPQMADAAEVMAGIQRRPGVTYAALTP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 109 NLKGFEAA-----------------------------------------------------------------------V 117
Cdd:PRK05692  81 NLKGLEAAlaagadevavfasaseafsqknincsiaeslerfepvaeaakqagvrvrgyvscvlgcpyegevppeavadV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 118 TKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPY 197
Cdd:PRK05692 161 AERLFALGCYEISLGDTIGVGTPGQVRAVLEAVLAEFPAERLAGHFHDTYGQALANIYASLEEGITVFDASVGGLGGCPY 240

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 260654708 198 AQGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQALNRKTS 244
Cdd:PRK05692 241 APGASGNVATEDVLYMLHGLGIETGIDLDKLVRAGQFIQSKLGRPLP 287
DRE_TIM_metallolyase cd03174
DRE-TIM metallolyase superfamily; The DRE-TIM metallolyase superfamily includes ...
 36-237 4.70e-74

DRE-TIM metallolyase superfamily; The DRE-TIM metallolyase superfamily includes 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163674 [Multi-domain]  Cd Length: 265  Bit Score: 226.18  E-value: 4.70e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  36 VEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKF-PGINYPVLTPN-LKGF 113
Cdd:cd03174    1 TDTTLRDGLQSEGATFSTEDKLEIAEALDEAGVDSIEVGSGASPKAVPQMEDDWEVLRAIRKLvPNVKLQALVRNrEKGI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 114 EAA-------------------------------------------------------------------VTKKFYSMGC 126
Cdd:cd03174   81 ERAleagvdevrifdsasethsrknlnksreedlenaeeaieaakeaglevegsledafgcktdpeyvleVAKALEEAGA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 127 YEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGgcpyaqGASGNLA 206
Cdd:cd03174  161 DEISLKDTVGLATPEEVAELVKALREALPDVPLGLHTHNTLGLAVANSLAALEAGADRVDGSVNGLG------ERAGNAA 234

                        250       260       270
                 ....*....|....*....|....*....|.
gi 260654708 207 TEDLVYMLEGLGIHTGVNLQKLLEAGNFICQ 237
Cdd:cd03174  235 TEDLVAALEGLGIDTGIDLEKLLEISRYVEE 265
HMGL-like pfam00682
HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and ...
 32-235 1.44e-61

HMGL-like; This family contains a diverse set of enzymes. These include various aldolases and a region of pyruvate carboxylase.


Pssm-ID: 459902 [Multi-domain]  Cd Length: 264  Bit Score: 194.48  E-value: 1.44e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708   32 RVKIVEVGPRDGLQNEKNIVSTPVKIKLIDMLSEAGLSVIETtsfvspkWVPQMG-DHTEVLKGIQKFPGIN--YPVLTP 108
Cdd:pfam00682   1 AVAICDTTLRDGEQALGVAFSIDEKLAIARALDAAGVDEIEV-------GFPAASeDDFEVVRAIAKVIPHAriLVLCRA 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  109 NLKGFEAAV---------------------------------------------------------------------TK 119
Cdd:pfam00682  74 REHDIKAAVealkgagavrvhvfiatsdlhrkyklgkdreevakravaavkaarsrgidvefspedasrtdpeflaevVE 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708  120 KFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVP-LAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGgcpya 198
Cdd:pfam00682 154 AAIEAGATRINIPDTVGVLTPNEAAELISALKARVPnKAIISVHCHNDLGMAVANSLAAVEAGADRVDGTVNGIG----- 228

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 260654708  199 qGASGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFI 235
Cdd:pfam00682 229 -ERAGNAALEEVAAALEGLGVDTGLDLQRLRSIANLV 264
LeuA COG0119
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; ...
 129-242 6.77e-17

Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; Isopropylmalate/homocitrate/citramalate synthases is part of the Pathway/BioSystem: Isoleucine, leucine, valine biosynthesis


Pssm-ID: 439889 [Multi-domain]  Cd Length: 452  Bit Score: 79.44  E-value: 6.77e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 129 ISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGG-CpyaqgasGNLAT 207
Cdd:COG0119  165 INLPDTVGGATPNEVADLIEELRERVPDVILSVHCHNDLGLAVANSLAAVEAGADQVEGTINGIGErA-------GNAAL 237

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 260654708 208 EDLV---YMLegLGIHTGVNLQKLLEAGNFICQALNRK 242
Cdd:COG0119  238 EEVVmnlKLK--YGVDTGIDLSKLTELSRLVSEITGLP 273
DRE_TIM_PC_TC_5S cd07937
Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain; This family includes ...
 117-231 3.13e-16

Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain; This family includes the carboxyltransferase domains of pyruvate carboxylase (PC) and the transcarboxylase (TC) 5S subunit. Transcarboxylase 5S is a cobalt-dependent metalloenzyme subunit of the biotin-dependent transcarboxylase multienzyme complex. Transcarboxylase 5S transfers carbon dioxide from the 1.3S biotin to pyruvate in the second of two carboxylation reactions catalyzed by TC. The first reaction involves the transfer of carbon dioxide from methylmalonyl-CoA to the 1.3S biotin, and is catalyzed by the 12S subunit. These two steps allow a carboxylate group to be transferred from oxaloacetate to propionyl-CoA to yield pyruvate and methylmalonyl-CoA. The catalytic domain of transcarboxylase 5S has a canonical TIM-barrel fold with a large C-terminal extension that forms a funnel leading to the active site. Transcarboxylase 5S forms a homodimer and there are six dimers per complex. In addition to the catalytic domain, transcarboxylase 5S has several other domains including a carbamoyl-phosphate synthase domain, a biotin carboxylase domain, a carboxyltransferase domain, and an ATP-grasp domain. Pyruvate carboxylase, like TC, is a biotin-dependent enzyme that catalyzes the carboxylation of pyruvate to produce oxaloacetate. In mammals, PC has critical roles in gluconeogenesis, lipogenesis, glyceroneogenesis, and insulin secretion. Inherited PC deficiencies are linked to serious diseases in humans such as lactic acidemia, hypoglycemia, psychomotor retardation, and death. PC is a single-chain enzyme and is active only in its homotetrameric form. PC has three domains, an N-terminal biotin carboxylase domain, a carboxyltransferase domain (this alignment model), and a C-terminal biotin-carboxyl carrier protein domain. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163675  Cd Length: 275  Bit Score: 75.93  E-value: 3.13e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 117 VTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAaLAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCp 196
Cdd:cd07937  154 LAKELEDMGADSICIKDMAGLLTPYAAYELVKALKKEVGLP-IHLHTHDTSGLAVATYLAAAEAGVDIVDTAISPLSGG- 231

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 260654708 197 YAQGasgnlATEDLVYMLEGLGIHTGVNLQKLLEA 231
Cdd:cd07937  232 TSQP-----STESMVAALRGTGRDTGLDLEKLEEI 261
DRE_TIM_HOA cd07943
4-hydroxy-2-oxovalerate aldolase, N-terminal catalytic TIM barrel domain; 4-hydroxy ...
 115-235 8.01e-16

4-hydroxy-2-oxovalerate aldolase, N-terminal catalytic TIM barrel domain; 4-hydroxy 2-ketovalerate aldolase (Also known as 4-hydroxy-2-ketovalerate aldolase and 4-hydroxy-2-oxopentanoate aldolase (HOA)) converts 4-hydroxy-2-oxopentanoate to acetaldehyde and pyruvate, the penultimate step in the meta-cleavage pathway for the degradation of phenols, cresols and catechol. This family includes the Escherichia coli MhpE aldolase, the Pseudomonas DmpG aldolase, and the Burkholderia xenovorans BphI pyruvate aldolase. In Pseudomonas, the DmpG aldolase tightly associates with a dehydrogenase (DmpF ) and is inactive without it. HOA has a canonical TIM-barrel fold with a C-terminal extension that forms a funnel leading to the active site. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163681  Cd Length: 263  Bit Score: 74.46  E-value: 8.01e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 115 AAVTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGG 194
Cdd:cd07943  144 AEQAKLMESYGADCVYVTDSAGAMLPDDVRERVRALREALDPTPVGFHGHNNLGLAVANSLAAVEAGATRIDGSLAGLGA 223

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 260654708 195 CpyaqgaSGNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFI 235
Cdd:cd07943  224 G------AGNTPLEVLVAVLERMGIETGIDLYKLMDAAEDL 258
DRE_TIM_IPMS cd07940
2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate ...
 125-231 9.39e-16

2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate synthase (IPMS) catalyzes an aldol-type condensation of acetyl-CoA and 2-oxoisovalerate yielding 2-isopropylmalate and CoA, the first committed step in leucine biosynthesis. This family includes the Arabidopsis thaliana IPMS1 and IPMS2 proteins, the Glycine max GmN56 protein, and the Brassica insularis BatIMS protein. This family also includes a group of archeal IPMS-like proteins represented by the Methanocaldococcus jannaschii AksA protein. AksA catalyzes the condensation of alpha-ketoglutarate and acetyl-CoA to form trans-homoaconitate, one of 13 steps in the conversion of alpha-ketoglutarate and acetylCoA to alpha-ketosuberate, a precursor to coenzyme B and biotin. AksA also catalyzes the condensation of alpha-ketoadipate or alpha-ketopimelate with acetylCoA to form, respectively, the (R)-homocitrate homologs (R)-2-hydroxy-1,2,5-pentanetricarboxylic acid and (R)-2-hydroxy-1,2,6- hexanetricarboxylic acid. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163678  Cd Length: 268  Bit Score: 74.41  E-value: 9.39e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 125 GCYEISLGDTIGVGTPGIMKDMLSAVMQEVP--LAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGgcpyaqGAS 202
Cdd:cd07940  156 GATTINIPDTVGYLTPEEFGELIKKLKENVPniKVPISVHCHNDLGLAVANSLAAVEAGARQVECTINGIG------ERA 229

                         90       100       110
                 ....*....|....*....|....*....|...
gi 260654708 203 GNLATEDLV----YMLEGLGIHTGVNLQKLLEA 231
Cdd:cd07940  230 GNAALEEVVmalkTRYDYYGVETGIDTEELYET 262
aksA PRK11858
trans-homoaconitate synthase; Reviewed
 119-242 1.74e-13

trans-homoaconitate synthase; Reviewed


Pssm-ID: 183341 [Multi-domain]  Cd Length: 378  Bit Score: 69.05  E-value: 1.74e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 119 KKFY----SMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAaLAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGg 194
Cdd:PRK11858 148 IEFAkaaeEAGADRVRFCDTVGILDPFTMYELVKELVEAVDIP-IEVHCHNDFGMATANALAGIEAGAKQVHTTVNGLG- 225

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 260654708 195 cpyaqGASGNLATEDLVYMLEGL-GIHTGVNLQKLLEAGNFICQALNRK 242
Cdd:PRK11858 226 -----ERAGNAALEEVVMALKYLyGIDLGIDTERLYELSRLVSKASGIP 269
PRK09282 PRK09282
pyruvate carboxylase subunit B; Validated
 119-233 4.23e-13

pyruvate carboxylase subunit B; Validated


Pssm-ID: 236449 [Multi-domain]  Cd Length: 592  Bit Score: 68.33  E-value: 4.23e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 119 KKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAaLAVHCHDTYGQALANTLMALQMGVSVVDSSVAglggcPYA 198
Cdd:PRK09282 161 KELEEMGCDSICIKDMAGLLTPYAAYELVKALKEEVDLP-VQLHSHCTSGLAPMTYLKAVEAGVDIIDTAIS-----PLA 234

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 260654708 199 QGASgNLATEDLVYMLEGLGIHTGVNLQKLLEAGN 233
Cdd:PRK09282 235 FGTS-QPPTESMVAALKGTPYDTGLDLELLFEIAE 268
PRK00915 PRK00915
2-isopropylmalate synthase; Validated
 129-251 2.68e-12

2-isopropylmalate synthase; Validated


Pssm-ID: 234864 [Multi-domain]  Cd Length: 513  Bit Score: 65.90  E-value: 2.68e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 129 ISLGDTIGVGTPGIMKDMLSAVMQEVP---LAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGgcpyaQGAsGNL 205
Cdd:PRK00915 166 INIPDTVGYTTPEEFGELIKTLRERVPnidKAIISVHCHNDLGLAVANSLAAVEAGARQVECTINGIG-----ERA-GNA 239

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 260654708 206 ATEDLVYML----EGLGIHTGVNLQKLLEagnficqalnrkTSSKVAQAT 251
Cdd:PRK00915 240 ALEEVVMALktrkDIYGVETGINTEEIYR------------TSRLVSQLT 277
PRK12331 PRK12331
oxaloacetate decarboxylase subunit alpha;
117-230 9.13e-12

oxaloacetate decarboxylase subunit alpha;


Pssm-ID: 183446 [Multi-domain]  Cd Length: 448  Bit Score: 64.34  E-value: 9.13e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 117 VTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAaLAVHCHDTYGQALANTLMALQMGVSVVDSSVAglggcP 196
Cdd:PRK12331 159 LAKEMQEMGADSICIKDMAGILTPYVAYELVKRIKEAVTVP-LEVHTHATSGIAEMTYLKAIEAGADIIDTAIS-----P 232

                         90       100       110
                 ....*....|....*....|....*....|....
gi 260654708 197 YAQGASgNLATEDLVYMLEGLGIHTGVNLQKLLE 230
Cdd:PRK12331 233 FAGGTS-QPATESMVAALQDLGYDTGLDLEELSE 265
PRK08195 PRK08195
4-hyroxy-2-oxovalerate/4-hydroxy-2-oxopentanoic acid aldolase,; Validated
 115-231 1.26e-11

4-hyroxy-2-oxovalerate/4-hydroxy-2-oxopentanoic acid aldolase,; Validated


Pssm-ID: 181282 [Multi-domain]  Cd Length: 337  Bit Score: 63.31  E-value: 1.26e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 115 AAVTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEV-PLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLG 193
Cdd:PRK08195 147 AEQAKLMESYGAQCVYVVDSAGALLPEDVRDRVRALRAALkPDTQVGFHGHNNLGLGVANSLAAVEAGATRIDGSLAGLG 226

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 260654708 194 GcpyaqGAsGNLATEDLVYMLEGLGIHTGVNLQKLLEA 231
Cdd:PRK08195 227 A-----GA-GNTPLEVLVAVLDRMGWETGVDLYKLMDA 258
DRE_TIM_NifV cd07939
Streptomyces rubellomurinus FrbC and related proteins, catalytic TIM barrel domain; FrbC (NifV) ...
 133-250 1.61e-11

Streptomyces rubellomurinus FrbC and related proteins, catalytic TIM barrel domain; FrbC (NifV) of Streptomyces rubellomurinus catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate and CoA, a reaction similar to one catalyzed by homocitrate synthase. The gene encoding FrbC is one of several genes required for the biosynthesis of FR900098, a potent antimalarial antibiotic. This protein is also required for assembly of the nitrogenase MoFe complex but its exact role is unknown. This family also includes the NifV proteins of Heliobacterium chlorum and Gluconacetobacter diazotrophicus, which appear to be orthologous to FrbC. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163677 [Multi-domain]  Cd Length: 259  Bit Score: 62.52  E-value: 1.61e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 133 DTIGVGTPGIMKDMLSAVMQEVPLAaLAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGgcpyaQGAsGNLATEDLVY 212
Cdd:cd07939  160 DTVGILDPFTTYELIRRLRAATDLP-LEFHAHNDLGLATANTLAAVRAGATHVSVTVNGLG-----ERA-GNAALEEVVM 232

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 260654708 213 MLEGL-GIHTGVNLQKLLEagnfICQalnrktssKVAQA 250
Cdd:cd07939  233 ALKHLyGRDTGIDTTRLPE----LSQ--------LVARA 259
DRE_TIM_HOA_like cd07944
4-hydroxy-2-oxovalerate aldolase-like, N-terminal catalytic TIM barrel domain; This family of ...
 127-231 1.31e-10

4-hydroxy-2-oxovalerate aldolase-like, N-terminal catalytic TIM barrel domain; This family of bacterial enzymes is sequence-similar to 4-hydroxy-2-oxovalerate aldolase (HOA) but its exact function is unknown. This family includes the Bacteroides vulgatus Bvu_2661 protein and belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163682  Cd Length: 266  Bit Score: 59.88  E-value: 1.31e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 127 YEISLGDTIGVGTPGIMKDMLSAVMQEV-PLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGgcpyaQGAsGNL 205
Cdd:cd07944  153 DVFYIVDSFGSMYPEDIKRIISLLRSNLdKDIKLGFHAHNNLQLALANTLEAIELGVEIIDATVYGMG-----RGA-GNL 226

                         90       100
                 ....*....|....*....|....*.
gi 260654708 206 ATEDLVYMLEGLGIHTgVNLQKLLEA 231
Cdd:cd07944  227 PTELLLDYLNNKFGKK-YNLEPVLEL 251
PRK09389 PRK09389
(R)-citramalate synthase; Provisional
 133-243 1.42e-10

(R)-citramalate synthase; Provisional


Pssm-ID: 236493 [Multi-domain]  Cd Length: 488  Bit Score: 60.72  E-value: 1.42e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 133 DTIGVGTPGIMKDMLSAvMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGgcpyaqGASGNLATEDLVY 212
Cdd:PRK09389 164 DTVGILTPEKTYELFKR-LSELVKGPVSIHCHNDFGLAVANTLAALAAGADQVHVTINGIG------ERAGNASLEEVVM 236

                         90       100       110
                 ....*....|....*....|....*....|..
gi 260654708 213 MLEGL-GIHTGVNLQKLLEagnfICQALNRKT 243
Cdd:PRK09389 237 ALKHLyDVETGIKLEELYE----LSRLVSRLT 264
PRK14040 PRK14040
oxaloacetate decarboxylase subunit alpha;
117-230 7.20e-10

oxaloacetate decarboxylase subunit alpha;


Pssm-ID: 237592 [Multi-domain]  Cd Length: 593  Bit Score: 58.79  E-value: 7.20e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 117 VTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAaLAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLgGCP 196
Cdd:PRK14040 160 LAKQLEDMGVDSLCIKDMAGLLKPYAAYELVSRIKKRVDVP-LHLHCHATTGLSTATLLKAIEAGIDGVDTAISSM-SMT 237

                         90       100       110
                 ....*....|....*....|....*....|....
gi 260654708 197 YaqgasGNLATEDLVYMLEGLGIHTGVNLQKLLE 230
Cdd:PRK14040 238 Y-----GHSATETLVATLEGTERDTGLDILKLEE 266
PRK12330 PRK12330
methylmalonyl-CoA carboxytransferase subunit 5S;
119-231 8.56e-09

methylmalonyl-CoA carboxytransferase subunit 5S;


Pssm-ID: 183445 [Multi-domain]  Cd Length: 499  Bit Score: 55.54  E-value: 8.56e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 119 KKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEV-PLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGCPy 197
Cdd:PRK12330 162 KRLLDMGADSICIKDMAALLKPQPAYDIVKGIKEACgEDTRINLHCHSTTGVTLVSLMKAIEAGVDVVDTAISSMSLGP- 240

                         90       100       110
                 ....*....|....*....|....*....|....
gi 260654708 198 aqgasGNLATEDLVYMLEGLGIHTGVNLQKLLEA 231
Cdd:PRK12330 241 -----GHNPTESLVEMLEGTGYTTKLDMDRLLKI 269
DRE_TIM_LeuA3 cd07941
Desulfobacterium autotrophicum LeuA3 and related proteins, N-terminal catalytic TIM barrel ...
 129-193 4.27e-07

Desulfobacterium autotrophicum LeuA3 and related proteins, N-terminal catalytic TIM barrel domain; Desulfobacterium autotrophicum LeuA3 is sequence-similar to alpha-isopropylmalate synthase (LeuA) but its exact function is unknown. Members of this family have an N-terminal TIM barrel domain that belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163679  Cd Length: 273  Bit Score: 49.76  E-value: 4.27e-07
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 260654708 129 ISLGDTIGvGT-PGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLG 193
Cdd:cd07941  168 LVLCDTNG-GTlPHEIAEIVKEVRERLPGVPLGIHAHNDSGLAVANSLAAVEAGATQVQGTINGYG 232
DRE_TIM_HCS cd07948
Saccharomyces cerevisiae homocitrate synthase and related proteins, catalytic TIM barrel ...
 108-193 6.35e-07

Saccharomyces cerevisiae homocitrate synthase and related proteins, catalytic TIM barrel domain; Homocitrate synthase (HCS) catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate, the first step in the lysine biosynthesis pathway. This family includes the Yarrowia lipolytica LYS1 protein as well as the Saccharomyces cerevisiae LYS20 and LYS21 proteins. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163685  Cd Length: 262  Bit Score: 49.25  E-value: 6.35e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 108 PNLKGFEAAVTKkfysMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAaLAVHCHDTYGQALANTLMALQMGVSVVDS 187
Cdd:cd07948  141 VDLLRVYRAVDK----LGVNRVGIADTVGIATPRQVYELVRTLRGVVSCD-IEFHGHNDTGCAIANAYAALEAGATHIDT 215


                 ....*.
gi 260654708 188 SVAGLG 193
Cdd:cd07948  216 TVLGIG 221
PRK12581 PRK12581
oxaloacetate decarboxylase; Provisional
 104-238 1.85e-06

oxaloacetate decarboxylase; Provisional


Pssm-ID: 79056 [Multi-domain]  Cd Length: 468  Bit Score: 48.19  E-value: 1.85e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 104 PVLTPNlkgFEAAVTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAV--MQEVPlaaLAVHCHDTYGQALANTLMALQMG 181
Cdd:PRK12581 158 PVHTLN---YYLSLVKELVEMGADSICIKDMAGILTPKAAKELVSGIkaMTNLP---LIVHTHATSGISQMTYLAAVEAG 231

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 260654708 182 VSVVDSSVAglggcPYAQGASgNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFICQA 238
Cdd:PRK12581 232 ADRIDTALS-----PFSEGTS-QPATESMYLALKEAGYDITLDETLLEQAANHLRQA 282
PRK12999 PRK12999
pyruvate carboxylase; Reviewed
 161-228 2.48e-06

pyruvate carboxylase; Reviewed


Pssm-ID: 237263 [Multi-domain]  Cd Length: 1146  Bit Score: 48.21  E-value: 2.48e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 260654708  161 VHCHDTYGQALANTLMALQMGVSVVD---SSVAGLggcpYAQGASGNlatedLVYMLEGLGIHTGVNLQKL 228
Cdd:PRK12999  739 LHTHDTSGNGLATYLAAAEAGVDIVDvavASMSGL----TSQPSLNS-----IVAALEGTERDTGLDLDAI 800
DRE_TIM_CMS cd07945
Leptospira interrogans citramalate synthase (CMS) and related proteins, N-terminal catalytic ...
 129-235 2.54e-06

Leptospira interrogans citramalate synthase (CMS) and related proteins, N-terminal catalytic TIM barrel domain; Citramalate synthase (CMS) catalyzes the conversion of pyruvate and acetyl-CoA to (R)-citramalate in the first dedicated step of the citramalate pathway. Citramalate is only found in Leptospira interrogans and a few other microorganisms. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163683 [Multi-domain]  Cd Length: 280  Bit Score: 47.37  E-value: 2.54e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 129 ISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGgcpyaqGASGNLATE 208
Cdd:cd07945  164 IMLPDTLGILSPFETYTYISDMVKRYPNLHFDFHAHNDYDLAVANVLAAVKAGIKGLHTTVNGLG------ERAGNAPLA 237

                         90       100
                 ....*....|....*....|....*...
gi 260654708 209 DLVYML-EGLGIHTGVNLQKLLEAGNFI 235
Cdd:cd07945  238 SVIAVLkDKLKVKTNIDEKRLNRASRLV 265
PLN03228 PLN03228
methylthioalkylmalate synthase; Provisional
 125-229 3.98e-06

methylthioalkylmalate synthase; Provisional


Pssm-ID: 178767 [Multi-domain]  Cd Length: 503  Bit Score: 47.22  E-value: 3.98e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 125 GCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLA---ALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGgcpyaqGA 201
Cdd:PLN03228 252 GATSVGIADTVGINMPHEFGELVTYVKANTPGIddiVFSVHCHNDLGLATANTIAGICAGARQVEVTINGIG------ER 325

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 260654708 202 SGNLATEDLV--------YMLEGLgiHTGVNLQKLL 229
Cdd:PLN03228 326 SGNASLEEVVmalkcrgaYLMNGV--YTGIDTRQIM 359
PRK14042 PRK14042
pyruvate carboxylase subunit B; Provisional
 119-250 3.38e-05

pyruvate carboxylase subunit B; Provisional


Pssm-ID: 172536 [Multi-domain]  Cd Length: 596  Bit Score: 44.71  E-value: 3.38e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 119 KKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLaALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLGGcpya 198
Cdd:PRK14042 161 KKLAEMGCDSIAIKDMAGLLTPTVTVELYAGLKQATGL-PVHLHSHSTSGLASICHYEAVLAGCNHIDTAISSFSG---- 235

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 260654708 199 qGASgNLATEDLVYMLEGLGIHTGVNLQKLLEAGNFIcQALNRKTSSKVAQA 250
Cdd:PRK14042 236 -GAS-HPPTEALVAALTDTPYDTELDLNILLEIDDYF-KAVRKKYSQFESEA 284
PycA COG1038
Pyruvate carboxylase [Energy production and conversion]; Pyruvate carboxylase is part of the ...
 161-230 6.45e-05

Pyruvate carboxylase [Energy production and conversion]; Pyruvate carboxylase is part of the Pathway/BioSystem: Urea cycle


Pssm-ID: 440660 [Multi-domain]  Cd Length: 1144  Bit Score: 43.91  E-value: 6.45e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 260654708  161 VHCHDTYGQALANTLMALQMGVSVVD---SSVAGLGGCPyaqgasgNLATedLVYMLEGLGIHTGVNLQKLLE 230
Cdd:COG1038   739 LHTHDTSGNQLATYLAAIEAGVDIVDvalASMSGLTSQP-------SLNS--LVAALEGTERDTGLDLDALQE 802
PRK12344 PRK12344
putative alpha-isopropylmalate/homocitrate synthase family transferase; Provisional
 131-193 1.25e-04

putative alpha-isopropylmalate/homocitrate synthase family transferase; Provisional


Pssm-ID: 237068 [Multi-domain]  Cd Length: 524  Bit Score: 42.77  E-value: 1.25e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 260654708 131 LGDTIGvGT-PGIMKDMLSAVMQEVPlAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLG 193
Cdd:PRK12344 177 LCDTNG-GTlPHEVAEIVAEVRAAPG-VPLGIHAHNDSGCAVANSLAAVEAGARQVQGTINGYG 238
DRE_TIM_Re_CS cd07947
Clostridium kluyveri Re-citrate synthase and related proteins, catalytic TIM barrel domain; ...
 129-235 7.48e-04

Clostridium kluyveri Re-citrate synthase and related proteins, catalytic TIM barrel domain; Re-citrate synthase (Re-CS) is a Clostridium kluyveri enzyme that converts acetyl-CoA and oxaloacetate to citrate. In most organisms, this reaction is catalyzed by Si-citrate synthase which is Si-face stereospecific with respect to C-2 of oxaloacetate, and phylogenetically unrelated to Re-citrate synthase. Re-citrate synthase is also found in a few other strictly anaerobic organisms. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".


Pssm-ID: 163684  Cd Length: 279  Bit Score: 40.00  E-value: 7.48e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260654708 129 ISLGDTIGVGTP---------------GIMKDMlsavmqEVPLAALAVHCHDTYGQALANTLMALQMGVSVVDSSVAGLG 193
Cdd:cd07947  167 IRLCDTLGYGVPypgaslprsvpkiiyGLRKDC------GVPSENLEWHGHNDFYKAVANAVAAWLYGASWVNCTLLGIG 240

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 260654708 194 gcpyaqGASGNLATEDLVYMLEGL-GIHTGVNLQKLLEAGNFI 235
Cdd:cd07947  241 ------ERTGNCPLEAMVIEYAQLkGNFDGMNLEVITEIAEYF 277
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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