NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|2293580160|gb|UVX50803|]
View 

MAG: Thymidylate synthase complementing protein [Bacteriophage sp.]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
ThyX cd20175
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
 126-249 1.99e-18

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: 80.94  E-value: 1.99e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2293580160 126 FHMMRYTFCVDTQISTSRELNRVSPNSIAEKSTRYVYEDGSICRPHWVSKEEAELfnndnnadldeaMNIYLNGCKRDFE 205
Cdd:cd20175    54 LEHASFTFEIEGVSAATHQLVRHRIASFTQESQRYVDLSGFKYPPPPPEIEDEEL------------EELYEEAMEEAEE 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2293580160 206 EYKILVDKyKIHRQDARGKLPLDTATRCIYTYSVREWRHIIDLR 249
Cdd:cd20175   122 LYEKLLEA-GIAKEDARYVLPNATKTRIVVTMNLRELLHFLELR 164
 
Name Accession Description Interval E-value
ThyX cd20175
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
 126-249 1.99e-18

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: 80.94  E-value: 1.99e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2293580160 126 FHMMRYTFCVDTQISTSRELNRVSPNSIAEKSTRYVYEDGSICRPHWVSKEEAELfnndnnadldeaMNIYLNGCKRDFE 205
Cdd:cd20175    54 LEHASFTFEIEGVSAATHQLVRHRIASFTQESQRYVDLSGFKYPPPPPEIEDEEL------------EELYEEAMEEAEE 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2293580160 206 EYKILVDKyKIHRQDARGKLPLDTATRCIYTYSVREWRHIIDLR 249
Cdd:cd20175   122 LYEKLLEA-GIAKEDARYVLPNATKTRIVVTMNLRELLHFLELR 164
ThyX COG1351
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
 126-249 3.16e-15

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: 72.25  E-value: 3.16e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2293580160 126 FHMMRYTF-CVDTQISTSRELNR---VSPNsiaEKSTRYV-YEDGSICRPHWVSKEEaelfnndnnadldEAMNIYLNGC 200
Cdd:COG1351    57 FEHASFTFaIEGVSRAVTHQLVRhriASYS---QQSQRYVkLDDKEYYIPPEIAKNE-------------ELLEEYEEAM 120

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2293580160 201 KRDFEEYKILVDKyKIHRQDARGKLPLDTATRCIYTYSVREWRHIIDLR 249
Cdd:COG1351   121 EKAFEAYEELLER-GVAREDARYVLPNATETKIVVTMNLRELLHFLKLR 168
Thy1 pfam02511
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
 131-249 4.85e-13

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: 66.12  E-value: 4.85e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2293580160 131 YTFCVD-TQISTSRELNRVSPNSIAEKSTRYVYEDGsicRPHWVSKEEAElfnndNNADLDEAMNIYLNGCKRDFEEYKI 209
Cdd:pfam02511  50 FTFAIEgVSRSVARQLVRHRIASFSQQSQRYVDLDD---EEFVIPPEIAL-----RGAQSEELDELYEEAMEEAYEAYEE 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2293580160 210 LVDKyKIHRQDARGKLPLDTATRCIYTYSVREWRHIIDLR 249
Cdd:pfam02511 122 LLEA-GVAREDARYVLPNATETRIVVTMNARSLLHFLELR 160
thyX TIGR02170
thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ...
 126-249 9.80e-09

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: 54.28  E-value: 9.80e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2293580160 126 FHMMRYTFCV-DTQISTSRELNRVSPNSIAEKSTRYVYEDGSICRPHwvsKEEAELFNNDNNAD------LDEAMNIYLN 198
Cdd:TIGR02170  52 LEHASFTFEVkGASRSVAAQLTRHRIASYSVQSQRYVLLRNEAPEGE---RVVVPPSVNDTNLDekpeevVEKAYAEAED 128

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2293580160 199 GCKRDFEEYKILVDKyKIHRQDARGKLPLDTATRCIYTYSVREWRHIIDLR 249
Cdd:TIGR02170 129 HYRASYELYRKLLEA-GIAREDARFVLPNALYTHIVVTGNARSLMHFLDLR 178
 
Name Accession Description Interval E-value
ThyX cd20175
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
 126-249 1.99e-18

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: 80.94  E-value: 1.99e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2293580160 126 FHMMRYTFCVDTQISTSRELNRVSPNSIAEKSTRYVYEDGSICRPHWVSKEEAELfnndnnadldeaMNIYLNGCKRDFE 205
Cdd:cd20175    54 LEHASFTFEIEGVSAATHQLVRHRIASFTQESQRYVDLSGFKYPPPPPEIEDEEL------------EELYEEAMEEAEE 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2293580160 206 EYKILVDKyKIHRQDARGKLPLDTATRCIYTYSVREWRHIIDLR 249
Cdd:cd20175   122 LYEKLLEA-GIAKEDARYVLPNATKTRIVVTMNLRELLHFLELR 164
ThyX COG1351
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
 126-249 3.16e-15

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: 72.25  E-value: 3.16e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2293580160 126 FHMMRYTF-CVDTQISTSRELNR---VSPNsiaEKSTRYV-YEDGSICRPHWVSKEEaelfnndnnadldEAMNIYLNGC 200
Cdd:COG1351    57 FEHASFTFaIEGVSRAVTHQLVRhriASYS---QQSQRYVkLDDKEYYIPPEIAKNE-------------ELLEEYEEAM 120

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2293580160 201 KRDFEEYKILVDKyKIHRQDARGKLPLDTATRCIYTYSVREWRHIIDLR 249
Cdd:COG1351   121 EKAFEAYEELLER-GVAREDARYVLPNATETKIVVTMNLRELLHFLKLR 168
Thy1 pfam02511
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
 131-249 4.85e-13

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: 66.12  E-value: 4.85e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2293580160 131 YTFCVD-TQISTSRELNRVSPNSIAEKSTRYVYEDGsicRPHWVSKEEAElfnndNNADLDEAMNIYLNGCKRDFEEYKI 209
Cdd:pfam02511  50 FTFAIEgVSRSVARQLVRHRIASFSQQSQRYVDLDD---EEFVIPPEIAL-----RGAQSEELDELYEEAMEEAYEAYEE 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2293580160 210 LVDKyKIHRQDARGKLPLDTATRCIYTYSVREWRHIIDLR 249
Cdd:pfam02511 122 LLEA-GVAREDARYVLPNATETRIVVTMNARSLLHFLELR 160
thyX TIGR02170
thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ...
 126-249 9.80e-09

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: 54.28  E-value: 9.80e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2293580160 126 FHMMRYTFCV-DTQISTSRELNRVSPNSIAEKSTRYVYEDGSICRPHwvsKEEAELFNNDNNAD------LDEAMNIYLN 198
Cdd:TIGR02170  52 LEHASFTFEVkGASRSVAAQLTRHRIASYSVQSQRYVLLRNEAPEGE---RVVVPPSVNDTNLDekpeevVEKAYAEAED 128

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2293580160 199 GCKRDFEEYKILVDKyKIHRQDARGKLPLDTATRCIYTYSVREWRHIIDLR 249
Cdd:TIGR02170 129 HYRASYELYRKLLEA-GIAREDARFVLPNALYTHIVVTGNARSLMHFLDLR 178
 
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