HTTP 200 OK
Allow: GET, HEAD
Content-Type: application/json
InterPro-Version: 108.0
InterPro-Version-Minor: 0
Vary: Accept
{
"metadata": {
"accession": "PS51330",
"entry_id": null,
"type": "domain",
"go_terms": null,
"source_database": "profile",
"member_databases": null,
"integrated": "IPR001796",
"hierarchy": null,
"name": {
"name": "Dihydrofolate reductase (DHFR) domain profile",
"short": "DHFR_2"
},
"description": [
{
"text": "<p>Dihydrofolate reductases (DHFRs) (EC 1.5.1.3) [1] are ubiquitous enzymes which\ncatalyze the NADPH-linked reduction of 7,8-dihydrofolate to 5,6,7,8-\ntetrahydrofolate. DHFRs are also capable of catalyzing the NADPH-linked\nreduction of folate to 7,8-dihydrofolate, but at a lesser rate, which varies\namong species. They can be inhibited by a number of antagonists such as\ntrimethroprim and methotrexate which are used as antibacterial or\nanticancerous agents.\n\nThymidylate synthase (TS) and DHFR catalyze sequential\nreactions in the thymidylate cycle, which supplies cells with their sole de\nnovo source of 2'-deoxythymidylate (dTMP) for DNA synthesis. TS catalyzes a\nreductive methylation of 2'deoxyuridylate (dUMP) to form dTMP in which the\ncofactor for the reaction, 5,10-methylenetetrahydrofolate is converted to\ndihydrofolate (FH(2)). DHFR then reduces FH(2) to tetrahydrofolate (FH(4)) in\na reaction requiring NADPH. In sources as diverse as bacteriophage,\nprokaryotes, fungi, mammalian viruses, and vertebrates, TS and DHFR are\ndistinct monofunctional enzymes. Protozoa and at least some plants are unusual\nin having a joined bifunctional polypetide that catalyzes both reactions\n[[cite:PUB00109616]][[cite:PUB00021881]].\n\nAn eight-stranded beta sheet consisting of seven parallel strands and a\ncarboxy-terminal antiparallel strand composes the core of the DHFR domain. The\nbeta-sheet core is flanked by alpha-helices [[cite:PUB00109616]][[cite:PUB00021881]][[cite:PUB00036579]][[cite:PUB00036593]][[cite:PUB00036596]].\n\nWe have derived a signature pattern from a region in the N-terminal part of\nthe DHFR domain, which includes a conserved Pro-Trp dipeptide; the tryptophan\nhas been shown [[cite:PUB00017878]] to be involved in the binding of substrate by the enzyme.\nWe have also developed a profile, which covers the entire DHFR domain.</p>",
"llm": false,
"checked": false,
"updated": false
}
],
"wikipedia": null,
"literature": {
"PUB00017878": {
"PMID": 3880743,
"ISBN": null,
"volume": "260",
"issue": "1",
"year": 1985,
"title": "Dihydrofolate reductase. The stereochemistry of inhibitor selectivity.",
"URL": null,
"raw_pages": "392-9",
"medline_journal": "J Biol Chem",
"ISO_journal": "J. Biol. Chem.",
"authors": [
"Matthews DA",
"Bolin JT",
"Burridge JM",
"Filman DJ",
"Volz KW",
"Kraut J."
],
"DOI_URL": "http://intl.jbc.org/cgi/content/abstract/260/1/392"
},
"PUB00109616": {
"PMID": 7656037,
"ISBN": null,
"volume": "1",
"issue": "3",
"year": 1994,
"title": "Structure of and kinetic channelling in bifunctional dihydrofolate reductase-thymidylate synthase.",
"URL": null,
"raw_pages": "186-94",
"medline_journal": "Nat Struct Biol",
"ISO_journal": "Nat Struct Biol",
"authors": [
"Knighton DR",
"Kan CC",
"Howland E",
"Janson CA",
"Hostomska Z",
"Welsh KM",
"Matthews DA."
],
"DOI_URL": null
},
"PUB00036579": {
"PMID": 2248959,
"ISBN": null,
"volume": "29",
"issue": "40",
"year": 1990,
"title": "Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate.",
"URL": null,
"raw_pages": "9467-79",
"medline_journal": "Biochemistry",
"ISO_journal": "Biochemistry",
"authors": [
"Davies JF 2nd",
"Delcamp TJ",
"Prendergast NJ",
"Ashford VA",
"Freisheim JH",
"Kraut J."
],
"DOI_URL": "http://dx.doi.org/10.1021/bi00492a021"
},
"PUB00036596": {
"PMID": 7873554,
"ISBN": null,
"volume": "34",
"issue": "8",
"year": 1995,
"title": "Isomorphous crystal structures of Escherichia coli dihydrofolate reductase complexed with folate, 5-deazafolate, and 5,10-dideazatetrahydrofolate: mechanistic implications.",
"URL": null,
"raw_pages": "2710-23",
"medline_journal": "Biochemistry",
"ISO_journal": "Biochemistry",
"authors": [
"Reyes VM",
"Sawaya MR",
"Brown KA",
"Kraut J."
],
"DOI_URL": "http://dx.doi.org/10.1021/bi00008a039"
},
"PUB00036593": {
"PMID": 1510919,
"ISBN": null,
"volume": "31",
"issue": "32",
"year": 1992,
"title": "Crystal structure of chicken liver dihydrofolate reductase complexed with NADP+ and biopterin.",
"URL": null,
"raw_pages": "7264-73",
"medline_journal": "Biochemistry",
"ISO_journal": "Biochemistry",
"authors": [
"McTigue MA",
"Davies JF 2nd",
"Kaufman BT",
"Kraut J."
],
"DOI_URL": "http://dx.doi.org/10.1021/bi00147a009"
},
"PUB00021881": {
"PMID": 12704428,
"ISBN": null,
"volume": "10",
"issue": "5",
"year": 2003,
"title": "Insights into antifolate resistance from malarial DHFR-TS structures.",
"URL": null,
"raw_pages": "357-65",
"medline_journal": "Nat Struct Biol",
"ISO_journal": "Nat. Struct. Biol.",
"authors": [
"Yuvaniyama J",
"Chitnumsub P",
"Kamchonwongpaisan S",
"Vanichtanankul J",
"Sirawaraporn W",
"Taylor P",
"Walkinshaw MD",
"Yuthavong Y."
],
"DOI_URL": "http://dx.doi.org/10.1038/nsb921"
}
},
"set_info": null,
"overlaps_with": null,
"counters": {
"subfamilies": 0,
"domain_architectures": 0,
"interactions": 0,
"matches": 30156,
"pathways": 0,
"proteins": 30141,
"proteomes": 17175,
"sets": 0,
"structural_models": {
"alphafold": 23871,
"bfvd": 21
},
"structures": 671,
"taxa": 32322
},
"entry_annotations": {},
"cross_references": {},
"is_llm": false,
"is_reviewed_llm": false,
"is_updated_llm": false,
"representative_structure": {
"accession": "1juv",
"name": "Crystal structure analysis of Dihydrofolate reductase from Bacteriophage T4"
}
}
}
