ID THI5_YEAST Reviewed; 340 AA. AC P43534; D6VTH2; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 24-JAN-2024, entry version 151. DE RecName: Full=4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase THI5 {ECO:0000303|PubMed:23048037}; DE Short=HMP-P synthase {ECO:0000303|PubMed:23048037}; DE Short=Hydroxymethylpyrimidine phosphate synthase {ECO:0000305}; DE EC=2.-.-.- {ECO:0000269|PubMed:23048037}; DE AltName: Full=Thiamine biosynthesis protein 5 {ECO:0000303|Ref.1}; DE AltName: Full=Thiamine pyrimidine synthase {ECO:0000250|UniProtKB:C4YMW2}; GN Name=THI5 {ECO:0000303|Ref.1}; GN Synonyms=MOL2 {ECO:0000303|PubMed:12777485}; GN OrderedLocusNames=YFL058W {ECO:0000312|SGD:S000001836}; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RA Hather R.J., Praekelt U., Meacock P.A.; RT "Characterisation of a new thiamine regulated Saccharomyces cerevisiae RT gene, THI5."; RL Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=7670463; DOI=10.1038/ng0795-261; RA Murakami Y., Naitou M., Hagiwara H., Shibata T., Ozawa M., Sasanuma S., RA Sasanuma M., Tsuchiya Y., Soeda E., Yokoyama K., Yamazaki M., Tashiro H., RA Eki T.; RT "Analysis of the nucleotide sequence of chromosome VI from Saccharomyces RT cerevisiae."; RL Nat. Genet. 10:261-268(1995). RN [3] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [4] RP THIAMINE BIOSYNTHESIS IN YEAST. RX PubMed=8528151; RA Tazuya K., Azumi C., Yamada K., Kumaoka H.; RT "Pyrimidine moiety of thiamin is biosynthesized from pyridoxine and RT histidine in Saccharomyces cerevisiae."; RL Biochem. Mol. Biol. Int. 36:883-888(1995). RN [5] RP PATHWAY. RX PubMed=12777485; DOI=10.1099/mic.0.26194-0; RA Wightman R., Meacock P.A.; RT "The THI5 gene family of Saccharomyces cerevisiae: distribution of RT homologues among the hemiascomycetes and functional redundancy in the RT aerobic biosynthesis of thiamin from pyridoxine."; RL Microbiology 149:1447-1460(2003). RN [6] RP THIAMINE BIOSYNTHESIS IN YEAST. RX PubMed=18388401; DOI=10.3177/jnsv.54.7; RA Ishida S., Tazuya-Murayama K., Kijima Y., Yamada K.; RT "The direct precursor of the pyrimidine moiety of thiamin is not urocanic RT acid but histidine in Saccharomyces cerevisiae."; RL J. Nutr. Sci. Vitaminol. 54:7-10(2008). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE, RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, MASS SPECTROMETRY, AND RP MUTAGENESIS OF ASN-11; TRP-12; LYS-62 AND HIS-66. RX PubMed=23048037; DOI=10.1074/jbc.m112.397240; RA Coquille S., Roux C., Fitzpatrick T.B., Thore S.; RT "The last piece in the vitamin B1 biosynthesis puzzle: structural and RT functional insight into yeast 4-amino-5-hydroxymethyl-2-methylpyrimidine RT phosphate (HMP-P) synthase."; RL J. Biol. Chem. 287:42333-42343(2012). CC -!- FUNCTION: Responsible for the formation of the pyrimidine heterocycle CC in the thiamine biosynthesis pathway. Catalyzes the formation of CC hydroxymethylpyrimidine phosphate (HMP-P) from histidine and pyridoxal CC phosphate (PLP). The protein uses PLP and the active site histidine to CC form HMP-P, generating an inactive enzyme. The enzyme can only undergo CC a single turnover, which suggests it is a suicide enzyme. CC {ECO:0000269|PubMed:23048037}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Fe(3+) + 4 H2O + L-histidyl-[4-amino-5-hydroxymethyl-2- CC methylpyrimidine phosphate synthase] + N(6)-(pyridoxal phosphate)-L- CC lysyl-[4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase] CC = (2S)-2-amino-5-hydroxy-4-oxopentanoyl-[4-amino-5-hydroxymethyl-2- CC methylpyrimidine phosphate synthase] + 3-oxopropanoate + 4-amino-2- CC methyl-5-(phosphooxymethyl)pyrimidine + 2 Fe(2+) + 2 H(+) + L-lysyl- CC [4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase]; CC Xref=Rhea:RHEA:65756, Rhea:RHEA-COMP:16892, Rhea:RHEA-COMP:16893, CC Rhea:RHEA-COMP:16894, Rhea:RHEA-COMP:16895, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, CC ChEBI:CHEBI:29969, ChEBI:CHEBI:29979, ChEBI:CHEBI:33190, CC ChEBI:CHEBI:58354, ChEBI:CHEBI:143915, ChEBI:CHEBI:157692; CC Evidence={ECO:0000269|PubMed:23048037}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65757; CC Evidence={ECO:0000269|PubMed:23048037}; CC -!- COFACTOR: CC Name=Fe cation; Xref=ChEBI:CHEBI:24875; CC Evidence={ECO:0000269|PubMed:23048037}; CC -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis. CC {ECO:0000305|PubMed:12777485}. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23048037}. CC -!- INTERACTION: CC P43534; P39940: RSP5; NbExp=2; IntAct=EBI-19221, EBI-16219; CC -!- MASS SPECTROMETRY: Mass=38513.4; Method=Electrospray; Note=This mass is CC that of the untagged protein plus the mass of an iron ion.; CC Evidence={ECO:0000269|PubMed:23048037}; CC -!- SIMILARITY: Belongs to the NMT1/THI5 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z48220; CAA88253.1; -; Genomic_DNA. DR EMBL; D50617; BAA09183.1; -; Genomic_DNA. DR EMBL; BK006940; DAA12382.1; -; Genomic_DNA. DR RefSeq; NP_116597.1; NM_001179909.1. DR PDB; 4H65; X-ray; 2.60 A; A/B=1-340. DR PDB; 4H67; X-ray; 2.70 A; A/B/C/D/E/F/G/H=1-340. DR PDB; 4H6D; X-ray; 2.90 A; A/B/C/D/E/F/G/H=1-340. DR PDBsum; 4H65; -. DR PDBsum; 4H67; -. DR PDBsum; 4H6D; -. DR AlphaFoldDB; P43534; -. DR SMR; P43534; -. DR BioGRID; 31089; 25. DR DIP; DIP-3951N; -. DR IntAct; P43534; 2. DR STRING; 4932.YFL058W; -. DR PaxDb; 4932-YFL058W; -. DR PeptideAtlas; P43534; -. DR EnsemblFungi; YFL058W_mRNA; YFL058W; YFL058W. DR GeneID; 850486; -. DR KEGG; sce:YFL058W; -. DR AGR; SGD:S000001836; -. DR SGD; S000001836; THI5. DR VEuPathDB; FungiDB:YFL058W; -. DR eggNOG; ENOG502QQ87; Eukaryota. DR GeneTree; ENSGT00940000176330; -. DR HOGENOM; CLU_028871_6_3_1; -. DR InParanoid; P43534; -. DR OMA; QHQEECK; -. DR OrthoDB; 45357at2759; -. DR BioCyc; MetaCyc:MONOMER3O-3915; -. DR BioCyc; YEAST:MONOMER3O-3915; -. DR BRENDA; 4.1.99.17; 984. DR UniPathway; UPA00060; -. DR PRO; PR:P43534; -. DR Proteomes; UP000002311; Chromosome VI. DR RNAct; P43534; Protein. DR GO; GO:0106344; F:4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase activity from histidine and PLP; IDA:UniProtKB. DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB. DR GO; GO:0009228; P:thiamine biosynthetic process; IDA:UniProtKB. DR GO; GO:0009229; P:thiamine diphosphate biosynthetic process; IEA:UniProtKB-UniPathway. DR CDD; cd13650; PBP2_THI5; 1. DR Gene3D; 3.40.190.10; Periplasmic binding protein-like II; 2. DR InterPro; IPR027939; NMT1/THI5. DR InterPro; IPR015168; SsuA/THI5. DR PANTHER; PTHR31528; 4-AMINO-5-HYDROXYMETHYL-2-METHYLPYRIMIDINE PHOSPHATE SYNTHASE THI11-RELATED; 1. DR PANTHER; PTHR31528:SF1; 4-AMINO-5-HYDROXYMETHYL-2-METHYLPYRIMIDINE PHOSPHATE SYNTHASE THI11-RELATED; 1. DR Pfam; PF09084; NMT1; 1. DR SUPFAM; SSF53850; Periplasmic binding protein-like II; 1. PE 1: Evidence at protein level; KW 3D-structure; Iron; Metal-binding; Pyridoxal phosphate; Reference proteome; KW Thiamine biosynthesis; Transferase. FT CHAIN 1..340 FT /note="4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate FT synthase THI5" FT /id="PRO_0000211618" FT MOTIF 195..199 FT /note="CCCFC; essential for catalytic activity, may be the FT site of iron coordination" FT /evidence="ECO:0000305|PubMed:23048037" FT ACT_SITE 66 FT /evidence="ECO:0000305|PubMed:23048037" FT BINDING 115..118 FT /ligand="pyridoxal 5'-phosphate" FT /ligand_id="ChEBI:CHEBI:597326" FT /evidence="ECO:0000269|PubMed:23048037" FT MOD_RES 62 FT /note="N6-(pyridoxal phosphate)lysine" FT /evidence="ECO:0000269|PubMed:23048037" FT MUTAGEN 11 FT /note="N->A: Unable to sustain growth in thiamine-free FT medium." FT /evidence="ECO:0000269|PubMed:23048037" FT MUTAGEN 12 FT /note="W->A: Unable to sustain growth in thiamine-free FT medium." FT /evidence="ECO:0000269|PubMed:23048037" FT MUTAGEN 62 FT /note="K->A: Unable to sustain growth in thiamine-free FT medium." FT /evidence="ECO:0000269|PubMed:23048037" FT MUTAGEN 66 FT /note="H->A: Unable to sustain growth in thiamine-free FT medium." FT /evidence="ECO:0000269|PubMed:23048037" FT MUTAGEN 195 FT /note="C->A: Attenuates the coordination of ion and is FT unable to sustain growth in thiamine-free medium." FT /evidence="ECO:0000269|PubMed:23048037" FT MUTAGEN 196 FT /note="C->A: Attenuates the coordination of ion and is FT unable to sustain growth in thiamine-free medium." FT /evidence="ECO:0000269|PubMed:23048037" FT MUTAGEN 197 FT /note="C->A: Attenuates the coordination of ion and is FT unable to sustain growth in thiamine-free medium." FT /evidence="ECO:0000269|PubMed:23048037" FT MUTAGEN 199 FT /note="C->A: Attenuates the coordination of ion and is FT unable to sustain growth in thiamine-free medium." FT /evidence="ECO:0000269|PubMed:23048037" FT STRAND 6..9 FT /evidence="ECO:0007829|PDB:4H65" FT STRAND 11..13 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 16..18 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 19..26 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 29..32 FT /evidence="ECO:0007829|PDB:4H65" FT STRAND 37..44 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 45..47 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 48..54 FT /evidence="ECO:0007829|PDB:4H65" FT STRAND 55..57 FT /evidence="ECO:0007829|PDB:4H65" FT STRAND 59..63 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 64..71 FT /evidence="ECO:0007829|PDB:4H65" FT TURN 72..74 FT /evidence="ECO:0007829|PDB:4H65" FT STRAND 77..84 FT /evidence="ECO:0007829|PDB:4H65" FT STRAND 89..94 FT /evidence="ECO:0007829|PDB:4H65" FT TURN 95..98 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 103..106 FT /evidence="ECO:0007829|PDB:4H65" FT STRAND 110..113 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 117..127 FT /evidence="ECO:0007829|PDB:4H67" FT TURN 128..130 FT /evidence="ECO:0007829|PDB:4H67" FT STRAND 135..140 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 142..144 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 145..150 FT /evidence="ECO:0007829|PDB:4H65" FT STRAND 153..160 FT /evidence="ECO:0007829|PDB:4H65" FT TURN 161..163 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 164..174 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 179..181 FT /evidence="ECO:0007829|PDB:4H65" FT STRAND 182..186 FT /evidence="ECO:0007829|PDB:4H65" FT STRAND 192..194 FT /evidence="ECO:0007829|PDB:4H6D" FT HELIX 196..199 FT /evidence="ECO:0007829|PDB:4H6D" FT STRAND 201..206 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 207..212 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 214..233 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 235..245 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 247..249 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 252..261 FT /evidence="ECO:0007829|PDB:4H65" FT TURN 262..264 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 273..285 FT /evidence="ECO:0007829|PDB:4H65" FT HELIX 315..330 FT /evidence="ECO:0007829|PDB:4H65" SQ SEQUENCE 340 AA; 38592 MW; D810C5D5A86FA6C0 CRC64; MSTDKITFLL NWQPTPYHIP IFLAQTKGYF KEQGLDMAIL EPTNPSDVTE LIGSGKVDMG LKAMIHTLAA KARGFPVTSV ASLLDEPFTG VLYLKGSGIT EDFQSLKGKK IGYVGEFGKI QIDELTKHYG MKPEDYTAVR CGMNVAKYII EGKIDAGIGI ECMQQVELEE YLAKQGRPAS DAKMLRIDKL ACLGCCCFCT VLYICNDEFL KKNPEKVRKF LKAIKKATDY VLADPVKAWK EYIDFKPQLN NDLSYKQYQR CYAYFSSSLY NVHRDWKKVT GYGKRLAILP PDYVSNYTNE YLSWPEPEEV SDPLEAQRLM AIHQEKCRQE GTFKRLALPA //