{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"O83033","secondaryAccessions":["Q56186"],"uniProtkbId":"FOMD_STRWE","entryAudit":{"firstPublicDate":"2024-01-24","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1998-11-01","entryVersion":61,"sequenceVersion":1},"annotationScore":4.0,"organism":{"scientificName":"Streptomyces wedmorensis","taxonId":43759,"lineage":["Bacteria","Bacillati","Actinomycetota","Actinomycetes","Kitasatosporales","Streptomycetaceae","Streptomyces"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Cytidylyl-2-hydroxypropylphosphonate hydrolase"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}],"value":"3.6.1.-"}]}},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7500951"}],"value":"fomD"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}],"value":"Involved in fosfomycin biosynthesis (PubMed:30010320). Catalyzes the hydrolysis of cytidylyl (S)-2-hydroxypropylphosphonate ((S)-HPP-CMP) to give (S)-2-hydroxypropylphosphonate ((S)-HPP) and CMP (PubMed:30010320). Can also hydrolyze (R)-HPP-CMP and cytidylyl 2-hydroxyethylphosphonate (HEP-CMP), which is a biosynthetic intermediate before C-methylation, but the catalytic efficiency is much higher with (S)-HPP-CMP (PubMed:30010320)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"cytidine 5'-({hydroxy[(S)-2-hydroxypropyl]phosphonoyl}phosphate) + H2O = (S)-2-hydroxypropylphosphonate + CMP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:77231"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:60377"},{"database":"ChEBI","id":"CHEBI:62246"},{"database":"ChEBI","id":"CHEBI:142877"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:77232"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}]}]},{"commentType":"COFACTOR","cofactors":[{"name":"Mn(2+)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29035"}},{"name":"Co(2+)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:48828"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}],"value":"Hydrolysis of (S)-HPP-CMP is inhibited by CDP"}],"commentType":"ACTIVITY REGULATION"},{"commentType":"BIOPHYSICOCHEMICAL PROPERTIES","kineticParameters":{"michaelisConstants":[{"constant":19.0,"unit":"uM","substrate":"(S)-HPP-CMP","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}]},{"constant":31.0,"unit":"uM","substrate":"(R)-HPP-CMP","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}]},{"constant":52.0,"unit":"uM","substrate":"HEP-CMP","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}]}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}],"value":"kcat is 75 sec(-1) with (S)-HPP-CMP as substrate. kcat is 19 sec(-1) with (R)-HPP-CMP as substrate. kcat is 20 sec(-1) with HEP-CMP as substrate."}]}}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}],"value":"Antibiotic biosynthesis; fosfomycin biosynthesis"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30010320"}],"value":"Monomer in solution"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the FomD family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":209,"modifier":"EXACT"}},"description":"Cytidylyl-2-hydroxypropylphosphonate hydrolase","featureId":"PRO_0000459580"},{"type":"Active site","location":{"start":{"value":144,"modifier":"EXACT"},"end":{"value":144,"modifier":"EXACT"}},"description":"Proton donor","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"D2SNF7"}]},{"type":"Binding site","location":{"start":{"value":111,"modifier":"EXACT"},"end":{"value":111,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:60240"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"D2SNF7"}],"ligand":{"name":"a divalent metal cation","id":"ChEBI:CHEBI:60240","label":"1"}},{"type":"Binding site","location":{"start":{"value":127,"modifier":"EXACT"},"end":{"value":127,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:60240"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"D2SNF7"}],"ligand":{"name":"a divalent metal cation","id":"ChEBI:CHEBI:60240","label":"1"}},{"type":"Binding site","location":{"start":{"value":129,"modifier":"EXACT"},"end":{"value":129,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:60240"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"D2SNF7"}],"ligand":{"name":"a divalent metal cation","id":"ChEBI:CHEBI:60240","label":"2"}},{"type":"Binding site","location":{"start":{"value":131,"modifier":"EXACT"},"end":{"value":131,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:60240"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"D2SNF7"}],"ligand":{"name":"a divalent metal cation","id":"ChEBI:CHEBI:60240","label":"1"}},{"type":"Binding site","location":{"start":{"value":131,"modifier":"EXACT"},"end":{"value":131,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:60240"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"D2SNF7"}],"ligand":{"name":"a divalent metal cation","id":"ChEBI:CHEBI:60240","label":"2"}},{"type":"Binding site","location":{"start":{"value":145,"modifier":"EXACT"},"end":{"value":145,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:60240"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"D2SNF7"}],"ligand":{"name":"a divalent metal cation","id":"ChEBI:CHEBI:60240","label":"2"}}],"keywords":[{"id":"KW-0045","category":"Biological process","name":"Antibiotic biosynthesis"},{"id":"KW-0170","category":"Ligand","name":"Cobalt"},{"id":"KW-0378","category":"Molecular function","name":"Hydrolase"},{"id":"KW-0464","category":"Ligand","name":"Manganese"},{"id":"KW-0479","category":"Ligand","name":"Metal-binding"}],"references":[{"referenceNumber":1,"citation":{"id":"7500951","citationType":"journal article","authors":["Hidaka T.","Goda M.","Kuzuyama T.","Takei N.","Hidaka M.","Seto H."],"citationCrossReferences":[{"database":"PubMed","id":"7500951"},{"database":"DOI","id":"10.1007/bf00290527"}],"title":"Cloning and nucleotide sequence of fosfomycin biosynthetic genes of Streptomyces wedmorensis.","publicationDate":"1995","journal":"Mol. Gen. Genet.","firstPage":"274","lastPage":"280","volume":"249"},"referencePositions":["NUCLEOTIDE SEQUENCE [GENOMIC DNA]"],"referenceComments":[{"value":"144-91","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"30010320","citationType":"journal article","authors":["Sato S.","Miyanaga A.","Kim S.Y.","Kuzuyama T.","Kudo F.","Eguchi T."],"citationCrossReferences":[{"database":"PubMed","id":"30010320"},{"database":"DOI","id":"10.1021/acs.biochem.8b00690"}],"title":"Biochemical and structural analysis of FomD that catalyzes the hydrolysis of cytidylyl (S)-2-hydroxypropylphosphonate in fosfomycin biosynthesis.","publicationDate":"2018","journal":"Biochemistry","firstPage":"4858","lastPage":"4866","volume":"57"},"referencePositions":["FUNCTION","CATALYTIC ACTIVITY","COFACTOR","ACTIVITY REGULATION","BIOPHYSICOCHEMICAL PROPERTIES","PATHWAY","SUBUNIT"]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"AB016934","properties":[{"key":"ProteinId","value":"BAA32492.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"RefSeq","id":"WP_051787062.1","properties":[{"key":"NucleotideSequenceId","value":"NZ_JBIRVY010000005.1"}]},{"database":"AlphaFoldDB","id":"O83033","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"O83033","properties":[{"key":"Description","value":"-"}]},{"database":"KEGG","id":"ag:BAA32492","properties":[{"key":"Description","value":"-"}]},{"database":"BioCyc","id":"MetaCyc:MONOMER-20589","properties":[{"key":"Description","value":"-"}]},{"database":"UniPathway","id":"UPA01071","properties":[{"key":"RectionId","value":"-"}]},{"database":"Gene3D","id":"2.40.380.10","properties":[{"key":"EntryName","value":"FomD-like"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR007295","properties":[{"key":"EntryName","value":"DUF402"}]},{"database":"InterPro","id":"IPR035930","properties":[{"key":"EntryName","value":"FomD-like_sf"}]},{"database":"InterPro","id":"IPR050212","properties":[{"key":"EntryName","value":"Ntdp-like"}]},{"database":"PANTHER","id":"PTHR39159","properties":[{"key":"EntryName","value":"-"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR39159:SF1","properties":[{"key":"EntryName","value":"UPF0374 PROTEIN YGAC"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF04167","properties":[{"key":"EntryName","value":"DUF402"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF159234","properties":[{"key":"EntryName","value":"FomD-like"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MAEVASQETEFAAFAFGSVVERRDELEGRPWISYPVRVVADTPELVAVYLSHGTLLTFGDGPFSWGPHPWGPFGDRWQSAGILQLHRPGRGHSVWVLRDADTGAFREWYVNVEAPWRRTPTGFSTLDHEIDLVVPADSRTLRWKDVEKFEERARIGHFSPEEATAIRTEAADVAREIAAGEQWWDTSWSRWEPPAGWHALLQSFETEGS","length":209,"molWeight":23716,"crc64":"167AC5B40F3F48B2","md5":"26BB2BA7BE9AA10E8692F15496132C60"},"extraAttributes":{"countByCommentType":{"FUNCTION":1,"CATALYTIC ACTIVITY":1,"COFACTOR":1,"ACTIVITY REGULATION":1,"BIOPHYSICOCHEMICAL PROPERTIES":1,"PATHWAY":1,"SUBUNIT":1,"SIMILARITY":1},"countByFeatureType":{"Chain":1,"Active site":1,"Binding site":6},"uniParcId":"UPI00000BB56A"}}