NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|2037173298|ref|YP_010060493|]
View 

thymidylate synthase [Mycobacterium phage BabyRay]

Protein Classification

FAD-dependent thymidylate synthase( domain architecture ID 12035490)

FAD-dependent thymidylate synthase catalyzes the formation of dTMP and tetrahydrofolate from dUMP and methylenetetrahydrofolate using a flavin coenzyme as the source of reducing equivalents, derived from NADPH

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
Thy1 pfam02511
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
 36-228 7.52e-64

Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) complements the thymidine growth requirement of the organizms in which it is found, but shows no homology to thymidylate synthase. The bacterial members of this family at least are flavin-dependent thymidylate synthases.


:

Pssm-ID: 460576  Cd Length: 186  Bit Score: 197.09  E-value: 7.52e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298  36 TEADDLAEFAGRNCYRSFNRPNPATAKNEDYLNHIIDSGHESVLEHASATFYIE-ASRSVLTELERHRHLSFSVVSQRYV 114
Cdd:pfam02511   2 TDPEKLIAAAARVCYGSSSKPDELEEKDEKLIRYLLRHGHGSPFEHASFTFAIEgVSRSVARQLVRHRIASFSQQSQRYV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298 115 DPVPLGFHIPPAIEELPGDQQKLAFVYmRNAVEESTRSYDRLVALyseaglprKKAREAARAVLPNMTNSPMVVTGNHRA 194
Cdd:pfam02511  82 DLDDEEFVIPPEIALRGAQSEELDELY-EEAMEEAYEAYEELLEA--------GVAREDARYVLPNATETRIVVTMNARS 152

                         170       180       190
                  ....*....|....*....|....*....|....
gi 2037173298 195 WRYVIKARWHEAADAEIRDLAAELLRQLREIAPN 228
Cdd:pfam02511 153 LLHFLELRCCPRAQWEIRELAEEMLEELKKVAPV 186
 
Name Accession Description Interval E-value
Thy1 pfam02511
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
 36-228 7.52e-64

Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) complements the thymidine growth requirement of the organizms in which it is found, but shows no homology to thymidylate synthase. The bacterial members of this family at least are flavin-dependent thymidylate synthases.


Pssm-ID: 460576  Cd Length: 186  Bit Score: 197.09  E-value: 7.52e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298  36 TEADDLAEFAGRNCYRSFNRPNPATAKNEDYLNHIIDSGHESVLEHASATFYIE-ASRSVLTELERHRHLSFSVVSQRYV 114
Cdd:pfam02511   2 TDPEKLIAAAARVCYGSSSKPDELEEKDEKLIRYLLRHGHGSPFEHASFTFAIEgVSRSVARQLVRHRIASFSQQSQRYV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298 115 DPVPLGFHIPPAIEELPGDQQKLAFVYmRNAVEESTRSYDRLVALyseaglprKKAREAARAVLPNMTNSPMVVTGNHRA 194
Cdd:pfam02511  82 DLDDEEFVIPPEIALRGAQSEELDELY-EEAMEEAYEAYEELLEA--------GVAREDARYVLPNATETRIVVTMNARS 152

                         170       180       190
                  ....*....|....*....|....*....|....
gi 2037173298 195 WRYVIKARWHEAADAEIRDLAAELLRQLREIAPN 228
Cdd:pfam02511 153 LLHFLELRCCPRAQWEIRELAEEMLEELKKVAPV 186
ThyX COG1351
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
 1-230 1.16e-61

Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; Thymidylate synthase ThyX, FAD-dependent family is part of the Pathway/BioSystem: Thymidylate biosynthesis


Pssm-ID: 440962  Cd Length: 197  Bit Score: 191.66  E-value: 1.16e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298   1 MKVQLIAHTVvntsvlsdlgfdrdtewdefgplintEADDLAEFAGRNCYRSFNRPNP----ATAKNEDYLNHIIDSGHE 76
Cdd:COG1351     1 MKVRLIDYTP--------------------------DPEDLIAAAARVSYSSKSLRELlkelSEEKAEKLIRRLLRHGHE 54

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298  77 SVLEHASATFYIE-ASRSVLTELERHRHLSFSVVSQRYVDPVPLGFHIPPAIEELPGdqqklafvymrnAVEESTRSYDR 155
Cdd:COG1351    55 SPFEHASFTFAIEgVSRAVTHQLVRHRIASYSQQSQRYVKLDDKEYYIPPEIAKNEE------------LLEEYEEAMEK 122

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2037173298 156 LVALYSEAgLPRKKAREAARAVLPNMTNSPMVVTGNHRAWRYVIKARWHEAADAEIRDLAAELLRQLREIAPNTY 230
Cdd:COG1351   123 AFEAYEEL-LERGVAREDARYVLPNATETKIVVTMNLRELLHFLKLRCCSHAQWEIRELAEAMLEELKKVAPLLF 196
thyX TIGR02170
thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ...
 38-232 5.09e-57

thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ThyA (2.1.1.45) and ThyX (2.1.1.148). This model describes ThyX, a homotetrameric flavoprotein. Both enzymes convert dUMP to dTMP. Under oxygen-limiting conditions, thyX can complement a thyA mutation. [Purines, pyrimidines, nucleosides, and nucleotides, 2'-Deoxyribonucleotide metabolism]


Pssm-ID: 274010  Cd Length: 209  Bit Score: 180.24  E-value: 5.09e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298  38 ADDLAEFAGRNCYRSFNRPNPATAKNEDYLNHIIDSGHESVLEHASATFYIE-ASRSVLTELERHRHLSFSVVSQRYVD- 115
Cdd:TIGR02170  11 PDALIVQAARVSYSSFEKDKPGTATDAGLIDYLLRHGHFSPLEHASFTFEVKgASRSVAAQLTRHRIASYSVQSQRYVLl 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298 116 --PVPLGFH--IPPAIEELPGDQQKlaFVYMRNAVEESTRSYDRLVALYSEAgLPRKKAREAARAVLPNMTNSPMVVTGN 191
Cdd:TIGR02170  91 rnEAPEGERvvVPPSVNDTNLDEKP--EEVVEKAYAEAEDHYRASYELYRKL-LEAGIAREDARFVLPNALYTHIVVTGN 167

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 2037173298 192 HRAWRYVIKARWHEAADAEIRDLAAELLRQLREIAPNTYQD 232
Cdd:TIGR02170 168 ARSLMHFLDLRASNDAQWEIRELAEAMLDIVKEVAPWVFEA 208
ThyX cd20175
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
 37-224 1.41e-45

FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to thymidylate synthase (ThyA); This family contains FAD-dependent thymidylate synthase (also known as ThyX, Thy1, FDTS or thymidylate synthase complementing protein), found in many microbial genomes including several human pathogens, but absent in humans. This protein is mechanistically and structurally unrelated to thymidylate synthase (TS or ThyA) found in mammals. ThyA and ThyX both produce de novo thymidylate or deoxythymidine 5'-monophosphate (dTMP), an essential DNA precursor. The classic ThyA catalyzes the reductive methylation of deoxyuridine 5'-monophosphate (dUMP) to form dTMP, with methylenetetrahydrofolate (CH2H4folate) serving as a one-carbon donor and as the source of reductive power. On the other hand, ThyX contains FAD, tightly bound by a novel fold, that mediates hydride transfer from NADPH during catalysis. Consequently, CH2H4folate serves only as a carbon donor and tetrahydrofolate (and not dihydrofolate as in the case of ThyA) is produced. The differences between the ThyX and ThyA is used for mechanism-based drugs to selectively inhibit FDTS and not have much effect on human and other eukaryotic TS. ThyX has been pursued for the development of new antibacterial agents against Mycobacterium tuberculosis, the causative agent of the widespread infectious disease tuberculosis (TB). It is also an attractive target for designing specific antibiotic drugs against many diseases such as ulcers, periodontal disease, and Lyme's disease, as well as biological warfare agents such as anthrax, botulism, and typhus.


Pssm-ID: 412038 [Multi-domain]  Cd Length: 186  Bit Score: 150.28  E-value: 1.41e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298  37 EADDLAEFAGRNCYRSFNRpNPATAKNEDYLNHIID-SGHESVLEHASATFYIEASRSVLTELERHRHLSFSVVSQRYVD 115
Cdd:cd20175    12 KPEELIAAAARVSYSSEGE-EKAEEEDEKLIKRLLKrDGHGSVLEHASFTFEIEGVSAATHQLVRHRIASFTQESQRYVD 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298 116 PVPLGFHIPPAIEELPGDQQKlafvyMRNAVEESTRSYDRLVAlyseaglpRKKAREAARAVLPNMTNSPMVVTGNHRAW 195
Cdd:cd20175    91 LSGFKYPPPPPEIEDEELEEL-----YEEAMEEAEELYEKLLE--------AGIAKEDARYVLPNATKTRIVVTMNLREL 157

                         170       180
                  ....*....|....*....|....*....
gi 2037173298 196 RYVIKARWHEAADAEIRDLAAELLRQLRE 224
Cdd:cd20175   158 LHFLELRTCPHAQWEIRELAEEMLEELKK 186
 
Name Accession Description Interval E-value
Thy1 pfam02511
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
 36-228 7.52e-64

Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) complements the thymidine growth requirement of the organizms in which it is found, but shows no homology to thymidylate synthase. The bacterial members of this family at least are flavin-dependent thymidylate synthases.


Pssm-ID: 460576  Cd Length: 186  Bit Score: 197.09  E-value: 7.52e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298  36 TEADDLAEFAGRNCYRSFNRPNPATAKNEDYLNHIIDSGHESVLEHASATFYIE-ASRSVLTELERHRHLSFSVVSQRYV 114
Cdd:pfam02511   2 TDPEKLIAAAARVCYGSSSKPDELEEKDEKLIRYLLRHGHGSPFEHASFTFAIEgVSRSVARQLVRHRIASFSQQSQRYV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298 115 DPVPLGFHIPPAIEELPGDQQKLAFVYmRNAVEESTRSYDRLVALyseaglprKKAREAARAVLPNMTNSPMVVTGNHRA 194
Cdd:pfam02511  82 DLDDEEFVIPPEIALRGAQSEELDELY-EEAMEEAYEAYEELLEA--------GVAREDARYVLPNATETRIVVTMNARS 152

                         170       180       190
                  ....*....|....*....|....*....|....
gi 2037173298 195 WRYVIKARWHEAADAEIRDLAAELLRQLREIAPN 228
Cdd:pfam02511 153 LLHFLELRCCPRAQWEIRELAEEMLEELKKVAPV 186
ThyX COG1351
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
 1-230 1.16e-61

Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; Thymidylate synthase ThyX, FAD-dependent family is part of the Pathway/BioSystem: Thymidylate biosynthesis


Pssm-ID: 440962  Cd Length: 197  Bit Score: 191.66  E-value: 1.16e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298   1 MKVQLIAHTVvntsvlsdlgfdrdtewdefgplintEADDLAEFAGRNCYRSFNRPNP----ATAKNEDYLNHIIDSGHE 76
Cdd:COG1351     1 MKVRLIDYTP--------------------------DPEDLIAAAARVSYSSKSLRELlkelSEEKAEKLIRRLLRHGHE 54

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298  77 SVLEHASATFYIE-ASRSVLTELERHRHLSFSVVSQRYVDPVPLGFHIPPAIEELPGdqqklafvymrnAVEESTRSYDR 155
Cdd:COG1351    55 SPFEHASFTFAIEgVSRAVTHQLVRHRIASYSQQSQRYVKLDDKEYYIPPEIAKNEE------------LLEEYEEAMEK 122

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2037173298 156 LVALYSEAgLPRKKAREAARAVLPNMTNSPMVVTGNHRAWRYVIKARWHEAADAEIRDLAAELLRQLREIAPNTY 230
Cdd:COG1351   123 AFEAYEEL-LERGVAREDARYVLPNATETKIVVTMNLRELLHFLKLRCCSHAQWEIRELAEAMLEELKKVAPLLF 196
thyX TIGR02170
thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ...
 38-232 5.09e-57

thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ThyA (2.1.1.45) and ThyX (2.1.1.148). This model describes ThyX, a homotetrameric flavoprotein. Both enzymes convert dUMP to dTMP. Under oxygen-limiting conditions, thyX can complement a thyA mutation. [Purines, pyrimidines, nucleosides, and nucleotides, 2'-Deoxyribonucleotide metabolism]


Pssm-ID: 274010  Cd Length: 209  Bit Score: 180.24  E-value: 5.09e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298  38 ADDLAEFAGRNCYRSFNRPNPATAKNEDYLNHIIDSGHESVLEHASATFYIE-ASRSVLTELERHRHLSFSVVSQRYVD- 115
Cdd:TIGR02170  11 PDALIVQAARVSYSSFEKDKPGTATDAGLIDYLLRHGHFSPLEHASFTFEVKgASRSVAAQLTRHRIASYSVQSQRYVLl 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298 116 --PVPLGFH--IPPAIEELPGDQQKlaFVYMRNAVEESTRSYDRLVALYSEAgLPRKKAREAARAVLPNMTNSPMVVTGN 191
Cdd:TIGR02170  91 rnEAPEGERvvVPPSVNDTNLDEKP--EEVVEKAYAEAEDHYRASYELYRKL-LEAGIAREDARFVLPNALYTHIVVTGN 167

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 2037173298 192 HRAWRYVIKARWHEAADAEIRDLAAELLRQLREIAPNTYQD 232
Cdd:TIGR02170 168 ARSLMHFLDLRASNDAQWEIRELAEAMLDIVKEVAPWVFEA 208
ThyX cd20175
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
 37-224 1.41e-45

FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to thymidylate synthase (ThyA); This family contains FAD-dependent thymidylate synthase (also known as ThyX, Thy1, FDTS or thymidylate synthase complementing protein), found in many microbial genomes including several human pathogens, but absent in humans. This protein is mechanistically and structurally unrelated to thymidylate synthase (TS or ThyA) found in mammals. ThyA and ThyX both produce de novo thymidylate or deoxythymidine 5'-monophosphate (dTMP), an essential DNA precursor. The classic ThyA catalyzes the reductive methylation of deoxyuridine 5'-monophosphate (dUMP) to form dTMP, with methylenetetrahydrofolate (CH2H4folate) serving as a one-carbon donor and as the source of reductive power. On the other hand, ThyX contains FAD, tightly bound by a novel fold, that mediates hydride transfer from NADPH during catalysis. Consequently, CH2H4folate serves only as a carbon donor and tetrahydrofolate (and not dihydrofolate as in the case of ThyA) is produced. The differences between the ThyX and ThyA is used for mechanism-based drugs to selectively inhibit FDTS and not have much effect on human and other eukaryotic TS. ThyX has been pursued for the development of new antibacterial agents against Mycobacterium tuberculosis, the causative agent of the widespread infectious disease tuberculosis (TB). It is also an attractive target for designing specific antibiotic drugs against many diseases such as ulcers, periodontal disease, and Lyme's disease, as well as biological warfare agents such as anthrax, botulism, and typhus.


Pssm-ID: 412038 [Multi-domain]  Cd Length: 186  Bit Score: 150.28  E-value: 1.41e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298  37 EADDLAEFAGRNCYRSFNRpNPATAKNEDYLNHIID-SGHESVLEHASATFYIEASRSVLTELERHRHLSFSVVSQRYVD 115
Cdd:cd20175    12 KPEELIAAAARVSYSSEGE-EKAEEEDEKLIKRLLKrDGHGSVLEHASFTFEIEGVSAATHQLVRHRIASFTQESQRYVD 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2037173298 116 PVPLGFHIPPAIEELPGDQQKlafvyMRNAVEESTRSYDRLVAlyseaglpRKKAREAARAVLPNMTNSPMVVTGNHRAW 195
Cdd:cd20175    91 LSGFKYPPPPPEIEDEELEEL-----YEEAMEEAEELYEKLLE--------AGIAKEDARYVLPNATKTRIVVTMNLREL 157

                         170       180
                  ....*....|....*....|....*....
gi 2037173298 196 RYVIKARWHEAADAEIRDLAAELLRQLRE 224
Cdd:cd20175   158 LHFLELRTCPHAQWEIRELAEEMLEELKK 186
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH