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Conserved domains on  [gi|472339658|ref|YP_007673191|]
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thymidylate synthase [Synechococcus phage S-RIP2]

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 ...
 19-223 5.70e-62

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: 192.57  E-value: 5.70e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658   19 SVKLIHSTPDGDNLVSYMARVSNPS---NQHNTETSARLIKYLIKHKHWSPFEMVNMCVEIT-TTRSIAAQILRHRSFSF 94
Cdd:TIGR02170   1 FVKLIDYTPGPDALIVQAARVSYSSfekDKPGTATDAGLIDYLLRHGHFSPLEHASFTFEVKgASRSVAAQLTRHRIASY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658   95 QEFSQRYAQV-TDKPEVPAFRRQDTVNRQNSTDDLElATVLEFELKTQSLYDLSYSLYEEMLQAGVAKECAREVLPMSSP 173
Cdd:TIGR02170  81 SVQSQRYVLLrNEAPEGERVVVPPSVNDTNLDEKPE-EVVEKAYAEAEDHYRASYELYRKLLEAGIAREDARFVLPNALY 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 472339658  174 TKLYMNGTLRSWIHYTDLRCANGTQHEHKLIADGCRDLIKQCFPQVFEAL 223
Cdd:TIGR02170 160 THIVVTGNARSLMHFLDLRASNDAQWEIRELAEAMLDIVKEVAPWVFEAF 209
 
Name Accession Description Interval E-value
thyX TIGR02170
thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ...
 19-223 5.70e-62

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: 192.57  E-value: 5.70e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658   19 SVKLIHSTPDGDNLVSYMARVSNPS---NQHNTETSARLIKYLIKHKHWSPFEMVNMCVEIT-TTRSIAAQILRHRSFSF 94
Cdd:TIGR02170   1 FVKLIDYTPGPDALIVQAARVSYSSfekDKPGTATDAGLIDYLLRHGHFSPLEHASFTFEVKgASRSVAAQLTRHRIASY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658   95 QEFSQRYAQV-TDKPEVPAFRRQDTVNRQNSTDDLElATVLEFELKTQSLYDLSYSLYEEMLQAGVAKECAREVLPMSSP 173
Cdd:TIGR02170  81 SVQSQRYVLLrNEAPEGERVVVPPSVNDTNLDEKPE-EVVEKAYAEAEDHYRASYELYRKLLEAGIAREDARFVLPNALY 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 472339658  174 TKLYMNGTLRSWIHYTDLRCANGTQHEHKLIADGCRDLIKQCFPQVFEAL 223
Cdd:TIGR02170 160 THIVVTGNARSLMHFLDLRASNDAQWEIRELAEAMLDIVKEVAPWVFEAF 209
ThyX COG1351
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
 20-221 7.26e-54

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: 171.25  E-value: 7.26e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658  20 VKLIHSTPDGDNLVSYMARVS-------NPSNQHNTETSARLIKYLIKHKHWSPFEMVNMCVEITTT-RSIAAQILRHRS 91
Cdd:COG1351    3 VRLIDYTPDPEDLIAAAARVSysskslrELLKELSEEKAEKLIRRLLRHGHESPFEHASFTFAIEGVsRAVTHQLVRHRI 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658  92 FSFQEFSQRYAQVTDKPEV-PAfrrqdtvnrqnstddlELATVLEFELKTQSLYDLSYSLYEEMLQAGVAKECAREVLPM 170
Cdd:COG1351   83 ASYSQQSQRYVKLDDKEYYiPP----------------EIAKNEELLEEYEEAMEKAFEAYEELLERGVAREDARYVLPN 146

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 472339658 171 SSPTKLYMNGTLRSWIHYTDLRCANGTQHEHKLIADGCRDLIKQCFPQVFE 221
Cdd:COG1351  147 ATETKIVVTMNLRELLHFLKLRCCSHAQWEIRELAEAMLEELKKVAPLLFE 197
Thy1 pfam02511
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
 28-217 5.28e-48

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: 155.88  E-value: 5.28e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658   28 DGDNLVSYMARVSNPSNQ---HNTETSARLIKYLIKHKHWSPFEMVNMCVEITTT-RSIAAQILRHRSFSFQEFSQRYAQ 103
Cdd:pfam02511   3 DPEKLIAAAARVCYGSSSkpdELEEKDEKLIRYLLRHGHGSPFEHASFTFAIEGVsRSVARQLVRHRIASFSQQSQRYVD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658  104 VTDKP-EVPAFRRQDTVNRQnstddlelatvlEFELKTQSLYDLSYSLYEEMLQAGVAKECAREVLPMSSPTKLYMNGTL 182
Cdd:pfam02511  83 LDDEEfVIPPEIALRGAQSE------------ELDELYEEAMEEAYEAYEELLEAGVAREDARYVLPNATETRIVVTMNA 150

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 472339658  183 RSWIHYTDLRCANGTQHEHKLIADGCRDLIKQCFP 217
Cdd:pfam02511 151 RSLLHFLELRCCPRAQWEIRELAEEMLEELKKVAP 185
ThyX cd20175
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
 21-214 2.15e-46

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: 151.82  E-value: 2.15e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658  21 KLIHSTPDGDN----LVSYMARVSNPSNQHN--TETSARLIKYLIK-HKHWSPFEMVNMCVEITTTRSIAAQILRHRSFS 93
Cdd:cd20175    1 ELIDYTPDPEEkpeeLIAAAARVSYSSEGEEkaEEEDEKLIKRLLKrDGHGSVLEHASFTFEIEGVSAATHQLVRHRIAS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658  94 FQEFSQRYAQVTDKPEVPafrrqdtvnrqnstdDLELATVLEFELKTQSLYDLSYSLYEEMLQAGVAKECAREVLPMSSP 173
Cdd:cd20175   81 FTQESQRYVDLSGFKYPP---------------PPPEIEDEELEELYEEAMEEAEELYEKLLEAGIAKEDARYVLPNATK 145

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 472339658 174 TKLYMNGTLRSWIHYTDLRCANGTQHEHKLIADGCRDLIKQ 214
Cdd:cd20175  146 TRIVVTMNLRELLHFLELRTCPHAQWEIRELAEEMLEELKK 186
 
Name Accession Description Interval E-value
thyX TIGR02170
thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ...
 19-223 5.70e-62

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: 192.57  E-value: 5.70e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658   19 SVKLIHSTPDGDNLVSYMARVSNPS---NQHNTETSARLIKYLIKHKHWSPFEMVNMCVEIT-TTRSIAAQILRHRSFSF 94
Cdd:TIGR02170   1 FVKLIDYTPGPDALIVQAARVSYSSfekDKPGTATDAGLIDYLLRHGHFSPLEHASFTFEVKgASRSVAAQLTRHRIASY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658   95 QEFSQRYAQV-TDKPEVPAFRRQDTVNRQNSTDDLElATVLEFELKTQSLYDLSYSLYEEMLQAGVAKECAREVLPMSSP 173
Cdd:TIGR02170  81 SVQSQRYVLLrNEAPEGERVVVPPSVNDTNLDEKPE-EVVEKAYAEAEDHYRASYELYRKLLEAGIAREDARFVLPNALY 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 472339658  174 TKLYMNGTLRSWIHYTDLRCANGTQHEHKLIADGCRDLIKQCFPQVFEAL 223
Cdd:TIGR02170 160 THIVVTGNARSLMHFLDLRASNDAQWEIRELAEAMLDIVKEVAPWVFEAF 209
ThyX COG1351
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
 20-221 7.26e-54

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: 171.25  E-value: 7.26e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658  20 VKLIHSTPDGDNLVSYMARVS-------NPSNQHNTETSARLIKYLIKHKHWSPFEMVNMCVEITTT-RSIAAQILRHRS 91
Cdd:COG1351    3 VRLIDYTPDPEDLIAAAARVSysskslrELLKELSEEKAEKLIRRLLRHGHESPFEHASFTFAIEGVsRAVTHQLVRHRI 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658  92 FSFQEFSQRYAQVTDKPEV-PAfrrqdtvnrqnstddlELATVLEFELKTQSLYDLSYSLYEEMLQAGVAKECAREVLPM 170
Cdd:COG1351   83 ASYSQQSQRYVKLDDKEYYiPP----------------EIAKNEELLEEYEEAMEKAFEAYEELLERGVAREDARYVLPN 146

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 472339658 171 SSPTKLYMNGTLRSWIHYTDLRCANGTQHEHKLIADGCRDLIKQCFPQVFE 221
Cdd:COG1351  147 ATETKIVVTMNLRELLHFLKLRCCSHAQWEIRELAEAMLEELKKVAPLLFE 197
Thy1 pfam02511
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
 28-217 5.28e-48

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: 155.88  E-value: 5.28e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658   28 DGDNLVSYMARVSNPSNQ---HNTETSARLIKYLIKHKHWSPFEMVNMCVEITTT-RSIAAQILRHRSFSFQEFSQRYAQ 103
Cdd:pfam02511   3 DPEKLIAAAARVCYGSSSkpdELEEKDEKLIRYLLRHGHGSPFEHASFTFAIEGVsRSVARQLVRHRIASFSQQSQRYVD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658  104 VTDKP-EVPAFRRQDTVNRQnstddlelatvlEFELKTQSLYDLSYSLYEEMLQAGVAKECAREVLPMSSPTKLYMNGTL 182
Cdd:pfam02511  83 LDDEEfVIPPEIALRGAQSE------------ELDELYEEAMEEAYEAYEELLEAGVAREDARYVLPNATETRIVVTMNA 150

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 472339658  183 RSWIHYTDLRCANGTQHEHKLIADGCRDLIKQCFP 217
Cdd:pfam02511 151 RSLLHFLELRCCPRAQWEIRELAEEMLEELKKVAP 185
ThyX cd20175
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
 21-214 2.15e-46

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: 151.82  E-value: 2.15e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658  21 KLIHSTPDGDN----LVSYMARVSNPSNQHN--TETSARLIKYLIK-HKHWSPFEMVNMCVEITTTRSIAAQILRHRSFS 93
Cdd:cd20175    1 ELIDYTPDPEEkpeeLIAAAARVSYSSEGEEkaEEEDEKLIKRLLKrDGHGSVLEHASFTFEIEGVSAATHQLVRHRIAS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 472339658  94 FQEFSQRYAQVTDKPEVPafrrqdtvnrqnstdDLELATVLEFELKTQSLYDLSYSLYEEMLQAGVAKECAREVLPMSSP 173
Cdd:cd20175   81 FTQESQRYVDLSGFKYPP---------------PPPEIEDEELEELYEEAMEEAEELYEKLLEAGIAKEDARYVLPNATK 145

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 472339658 174 TKLYMNGTLRSWIHYTDLRCANGTQHEHKLIADGCRDLIKQ 214
Cdd:cd20175  146 TRIVVTMNLRELLHFLELRTCPHAQWEIRELAEEMLEELKK 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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