Summary: Thymidylate synthase complementing protein
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Thymidylate synthase complementing protein Provide feedback
Thymidylate synthase complementing protein (Thy1) complements the thymidine growth requirement of the organisms in which it is found, but shows no homology to thymidylate synthase.
Fraser CM, Norris SJ, Weinstock GM, White O, Sutton GG, Dodson R, Gwinn M, Hickey EK, Clayton R, Ketchum KA, Sodergren E, Hardham JM, McLeod MP, Salzberg S, Peterson J, Khalak H, Richardson D, Howell JK, Chidambaram M, Utterback T, McDonald L, Artiach P, , Science 1998;281:375-388.: Complete genome sequence of Treponema pallidum, the syphilis spirochete [see comments] PUBMED:9665876 EPMC:9665876
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This tab holds annotation information from the InterPro database.
InterPro entry IPR003669
All cellular organisms need thymidylate (dTMP) for the replication of their chromosomes, as dTMP is required for the biosynthesis of dTTP, a building block of DNA. Cells can produce thymidylate either de novo from dUMP or incorporate thymidine using thymidine kinase. The de novo pathway of dTMP synthesis requires a specific enzyme, thymidylate synthase, which methylates dUMP at position 5 of the pyrimidine ring. There are two pathways for thymidylate synthesis, each utilising a different thymidylate synthase enzyme: ThyA (EC) and ThyX (EC) [PUBMED:15046578]. Both enzymes convert dUMP to dTMP, but there is no sequence identity between the two enzymes, and their mechanisms of action differ [PUBMED:15123820]. Only ThyX uses FAD as cofactor.
The well studied thyA proteins catalyse the reductive methylation reaction of dUMP, with methylenetetrahydrofolate (CH(2)H(4)folate) serving as one-carbon donor and as source of reductive power. On the other hand the thyX family of thymidylate synthases contains FAD that is tightly bound by a novel fold. FAD mediates hydride transfer from NADPH during catalysis. Consequently, in the reaction catalysed by thyX, CH(2)H(4)folate serves only as a carbon donor and tetrahydrofolate (and not dihydrofolate as in the case of thyA) is produced [PUBMED:12029065, PUBMED:16707489].
The thyX domain consists of a central alpha/beta domain and two alpha-helices located away from the central domain. The central domain is made up of a five-stranded antiparallel beta-sheet, flanked by six alpha-helices on one side of the sheet [PUBMED:16707489, PUBMED:12211025, PUBMED:12791256]. Sequence alignments reveal a specific sequence motif R-H-R-X(7)-S (thyX motif) common to this family of proteins [PUBMED:12029065].
This entry represents the flavin-dependent enzyme ThyX, which is a homotetramer bound to four FAD molecules. Under oxygen-limiting conditions, thyX can complement a thyA mutation [PUBMED:12791256].
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|Molecular function||thymidylate synthase (FAD) activity (GO:0050797)|
|flavin adenine dinucleotide binding (GO:0050660)|
|Biological process||dTMP biosynthetic process (GO:0006231)|
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|Seed source:||Pfam-B_1648 (release 5.4)|
|Author:||Mian N, Bateman A|
|Number in seed:||163|
|Number in full:||1591|
|Average length of the domain:||199.20 aa|
|Average identity of full alignment:||24 %|
|Average coverage of the sequence by the domain:||79.78 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||10|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Thy1 domain has been found. There are 90 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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