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Conserved domains on  [gi|1842004034|ref|YP_009791425|]
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thymidylate synthase [Synechococcus phage Bellamy]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
ThyX super family cl42216
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
 5-210 1.23e-63

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.


The actual alignment was detected with superfamily member TIGR02170:

Pssm-ID: 478033  Cd Length: 209  Bit Score: 196.42  E-value: 1.23e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034   5 PIKLISVTPDAEKHMAYCARVSNP----NNQENEKFSGLLKYCVKHQHWSIFEQAYMTLEI-NTTRGVAAQVLRHRSMTY 79
Cdd:TIGR02170   1 FVKLIDYTPGPDALIVQAARVSYSsfekDKPGTATDAGLIDYLLRHGHFSPLEHASFTFEVkGASRSVAAQLTRHRIASY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034  80 QEFSQRYADsslLAEEIPLPELRR-QDTKNRQNSiDDVDPFVVQKYEMLMQQHFKEAMDLYKKMLDDGIAKECARFVLPL 158
Cdd:TIGR02170  81 SVQSQRYVL---LRNEAPEGERVVvPPSVNDTNL-DEKPEEVVEKAYAEAEDHYRASYELYRKLLEAGIAREDARFVLPN 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1842004034 159 ATPTRLYMTGSVRSWIHYIELRSANGTQKEHMDIALGAKKIFCEQFPAVAEA 210
Cdd:TIGR02170 157 ALYTHIVVTGNARSLMHFLDLRASNDAQWEIRELAEAMLDIVKEVAPWVFEA 208
 
Name Accession Description Interval E-value
thyX TIGR02170
thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ...
 5-210 1.23e-63

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: 196.42  E-value: 1.23e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034   5 PIKLISVTPDAEKHMAYCARVSNP----NNQENEKFSGLLKYCVKHQHWSIFEQAYMTLEI-NTTRGVAAQVLRHRSMTY 79
Cdd:TIGR02170   1 FVKLIDYTPGPDALIVQAARVSYSsfekDKPGTATDAGLIDYLLRHGHFSPLEHASFTFEVkGASRSVAAQLTRHRIASY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034  80 QEFSQRYADsslLAEEIPLPELRR-QDTKNRQNSiDDVDPFVVQKYEMLMQQHFKEAMDLYKKMLDDGIAKECARFVLPL 158
Cdd:TIGR02170  81 SVQSQRYVL---LRNEAPEGERVVvPPSVNDTNL-DEKPEEVVEKAYAEAEDHYRASYELYRKLLEAGIAREDARFVLPN 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1842004034 159 ATPTRLYMTGSVRSWIHYIELRSANGTQKEHMDIALGAKKIFCEQFPAVAEA 210
Cdd:TIGR02170 157 ALYTHIVVTGNARSLMHFLDLRASNDAQWEIRELAEAMLDIVKEVAPWVFEA 208
ThyX COG1351
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
 6-209 2.43e-53

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: 169.70  E-value: 2.43e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034   6 IKLISVTPDAEKHMAYCARVS--------NPNNQENEKFSGLLKYCVKHQHWSIFEQAYMTLEI-NTTRGVAAQVLRHRS 76
Cdd:COG1351     3 VRLIDYTPDPEDLIAAAARVSysskslreLLKELSEEKAEKLIRRLLRHGHESPFEHASFTFAIeGVSRAVTHQLVRHRI 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034  77 MTYQEFSQRYADSSLLAEEIPlPELRRqdtknrqnsiddvDPFVVQKYEMLMQqhfkEAMDLYKKMLDDGIAKECARFVL 156
Cdd:COG1351    83 ASYSQQSQRYVKLDDKEYYIP-PEIAK-------------NEELLEEYEEAME----KAFEAYEELLERGVAREDARYVL 144

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1842004034 157 PLATPTRLYMTGSVRSWIHYIELRSANGTQKEHMDIALGAKKIFCEQFPAVAE 209
Cdd:COG1351   145 PNATETKIVVTMNLRELLHFLKLRCCSHAQWEIRELAEAMLEELKKVAPLLFE 197
Thy1 pfam02511
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
 14-206 5.32e-51

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: 163.19  E-value: 5.32e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034  14 DAEKHMAYCARVSNPNNQEN----EKFSGLLKYCVKHQHWSIFEQAYMTLEI-NTTRGVAAQVLRHRSMTYQEFSQRYAD 88
Cdd:pfam02511   3 DPEKLIAAAARVCYGSSSKPdeleEKDEKLIRYLLRHGHGSPFEHASFTFAIeGVSRSVARQLVRHRIASFSQQSQRYVD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034  89 SSLLAEEIPLPELRRQDtknrqnsiddVDPFVVQKYEmlmqQHFKEAMDLYKKMLDDGIAKECARFVLPLATPTRLYMTG 168
Cdd:pfam02511  83 LDDEEFVIPPEIALRGA----------QSEELDELYE----EAMEEAYEAYEELLEAGVAREDARYVLPNATETRIVVTM 148

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1842004034 169 SVRSWIHYIELRSANGTQKEHMDIALGAKKIFCEQFPA 206
Cdd:pfam02511 149 NARSLLHFLELRCCPRAQWEIRELAEEMLEELKKVAPV 186
ThyX cd20175
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
 7-202 2.15e-50

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: 161.83  E-value: 2.15e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034   7 KLISVTPDAEKHM----AYCARVSNPNNQEN---EKFSGLLKYCVK-HQHWSIFEQAYMTLEINTTRGVAAQVLRHRSMT 78
Cdd:cd20175     1 ELIDYTPDPEEKPeeliAAAARVSYSSEGEEkaeEEDEKLIKRLLKrDGHGSVLEHASFTFEIEGVSAATHQLVRHRIAS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034  79 YQEFSQRYADSSLLAEEIPLPELRRQDTKNrqnsiddvdpfvvqkyemLMQQHFKEAMDLYKKMLDDGIAKECARFVLPL 158
Cdd:cd20175    81 FTQESQRYVDLSGFKYPPPPPEIEDEELEE------------------LYEEAMEEAEELYEKLLEAGIAKEDARYVLPN 142

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1842004034 159 ATPTRLYMTGSVRSWIHYIELRSANGTQKEHMDIALGAKKIFCE 202
Cdd:cd20175   143 ATKTRIVVTMNLRELLHFLELRTCPHAQWEIRELAEEMLEELKK 186
 
Name Accession Description Interval E-value
thyX TIGR02170
thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ...
 5-210 1.23e-63

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: 196.42  E-value: 1.23e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034   5 PIKLISVTPDAEKHMAYCARVSNP----NNQENEKFSGLLKYCVKHQHWSIFEQAYMTLEI-NTTRGVAAQVLRHRSMTY 79
Cdd:TIGR02170   1 FVKLIDYTPGPDALIVQAARVSYSsfekDKPGTATDAGLIDYLLRHGHFSPLEHASFTFEVkGASRSVAAQLTRHRIASY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034  80 QEFSQRYADsslLAEEIPLPELRR-QDTKNRQNSiDDVDPFVVQKYEMLMQQHFKEAMDLYKKMLDDGIAKECARFVLPL 158
Cdd:TIGR02170  81 SVQSQRYVL---LRNEAPEGERVVvPPSVNDTNL-DEKPEEVVEKAYAEAEDHYRASYELYRKLLEAGIAREDARFVLPN 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1842004034 159 ATPTRLYMTGSVRSWIHYIELRSANGTQKEHMDIALGAKKIFCEQFPAVAEA 210
Cdd:TIGR02170 157 ALYTHIVVTGNARSLMHFLDLRASNDAQWEIRELAEAMLDIVKEVAPWVFEA 208
ThyX COG1351
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
 6-209 2.43e-53

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: 169.70  E-value: 2.43e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034   6 IKLISVTPDAEKHMAYCARVS--------NPNNQENEKFSGLLKYCVKHQHWSIFEQAYMTLEI-NTTRGVAAQVLRHRS 76
Cdd:COG1351     3 VRLIDYTPDPEDLIAAAARVSysskslreLLKELSEEKAEKLIRRLLRHGHESPFEHASFTFAIeGVSRAVTHQLVRHRI 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034  77 MTYQEFSQRYADSSLLAEEIPlPELRRqdtknrqnsiddvDPFVVQKYEMLMQqhfkEAMDLYKKMLDDGIAKECARFVL 156
Cdd:COG1351    83 ASYSQQSQRYVKLDDKEYYIP-PEIAK-------------NEELLEEYEEAME----KAFEAYEELLERGVAREDARYVL 144

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1842004034 157 PLATPTRLYMTGSVRSWIHYIELRSANGTQKEHMDIALGAKKIFCEQFPAVAE 209
Cdd:COG1351   145 PNATETKIVVTMNLRELLHFLKLRCCSHAQWEIRELAEAMLEELKKVAPLLFE 197
Thy1 pfam02511
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
 14-206 5.32e-51

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: 163.19  E-value: 5.32e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034  14 DAEKHMAYCARVSNPNNQEN----EKFSGLLKYCVKHQHWSIFEQAYMTLEI-NTTRGVAAQVLRHRSMTYQEFSQRYAD 88
Cdd:pfam02511   3 DPEKLIAAAARVCYGSSSKPdeleEKDEKLIRYLLRHGHGSPFEHASFTFAIeGVSRSVARQLVRHRIASFSQQSQRYVD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034  89 SSLLAEEIPLPELRRQDtknrqnsiddVDPFVVQKYEmlmqQHFKEAMDLYKKMLDDGIAKECARFVLPLATPTRLYMTG 168
Cdd:pfam02511  83 LDDEEFVIPPEIALRGA----------QSEELDELYE----EAMEEAYEAYEELLEAGVAREDARYVLPNATETRIVVTM 148

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1842004034 169 SVRSWIHYIELRSANGTQKEHMDIALGAKKIFCEQFPA 206
Cdd:pfam02511 149 NARSLLHFLELRCCPRAQWEIRELAEEMLEELKKVAPV 186
ThyX cd20175
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
 7-202 2.15e-50

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: 161.83  E-value: 2.15e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034   7 KLISVTPDAEKHM----AYCARVSNPNNQEN---EKFSGLLKYCVK-HQHWSIFEQAYMTLEINTTRGVAAQVLRHRSMT 78
Cdd:cd20175     1 ELIDYTPDPEEKPeeliAAAARVSYSSEGEEkaeEEDEKLIKRLLKrDGHGSVLEHASFTFEIEGVSAATHQLVRHRIAS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1842004034  79 YQEFSQRYADSSLLAEEIPLPELRRQDTKNrqnsiddvdpfvvqkyemLMQQHFKEAMDLYKKMLDDGIAKECARFVLPL 158
Cdd:cd20175    81 FTQESQRYVDLSGFKYPPPPPEIEDEELEE------------------LYEEAMEEAEELYEKLLEAGIAKEDARYVLPN 142

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1842004034 159 ATPTRLYMTGSVRSWIHYIELRSANGTQKEHMDIALGAKKIFCE 202
Cdd:cd20175   143 ATKTRIVVTMNLRELLHFLELRTCPHAQWEIRELAEEMLEELKK 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.
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