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
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
26-256
6.32e-32
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: 118.86 E-value: 6.32e-32
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
26-256
6.32e-32
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: 118.86 E-value: 6.32e-32
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
30-256
3.24e-27
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: 105.98 E-value: 3.24e-27
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
35-256
2.37e-26
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: 103.87 E-value: 2.37e-26
thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ...
28-256
5.28e-18
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: 81.63 E-value: 5.28e-18
Thymidylate synthase ThyX, FAD-dependent family [Nucleotide transport and metabolism]; ...
26-256
6.32e-32
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: 118.86 E-value: 6.32e-32
FAD-dependent thymidylate synthase (ThyX), mechanistically and structurally unrelated to ...
30-256
3.24e-27
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: 105.98 E-value: 3.24e-27
Thymidylate synthase complementing protein; Thymidylate synthase complementing protein (Thy1) ...
35-256
2.37e-26
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: 103.87 E-value: 2.37e-26
thymidylate synthase, flavin-dependent; Two forms of microbial thymidylate synthase are known: ...
28-256
5.28e-18
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: 81.63 E-value: 5.28e-18
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.
of the residues that compose this conserved feature have been mapped to the query sequence.
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