ID   NMT1_ASPPA              Reviewed;         342 AA.
AC   P42882;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   03-AUG-2022, entry version 58.
DE   RecName: Full=4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase {ECO:0000250|UniProtKB:P43534};
DE            Short=HMP-P synthase {ECO:0000250|UniProtKB:P43534};
DE            Short=Hydroxymethylpyrimidine phosphate synthase {ECO:0000250|UniProtKB:P43534};
DE            EC=2.-.-.- {ECO:0000250|UniProtKB:P43534};
DE   AltName: Full=Thiamine pyrimidine synthase {ECO:0000250|UniProtKB:C4YMW2};
GN   Name=nmt1 {ECO:0000303|PubMed:7711083};
OS   Aspergillus parasiticus.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX   NCBI_TaxID=5067;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC   STRAIN=ATCC 56775 / NRRL 5862 / Su-1 / SRRC 143;
RX   PubMed=7711083; DOI=10.1016/0167-4781(95)00032-c;
RA   Cary J.W., Bhatnagar D.;
RT   "Nucleotide sequence of an Aspergillus parasiticus gene strongly repressed
RT   by thiamine.";
RL   Biochim. Biophys. Acta 1261:319-320(1995).
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:0000250|UniProtKB:P43534}.
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:0000250|UniProtKB:P43534};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65757;
CC         Evidence={ECO:0000250|UniProtKB:P43534};
CC   -!- COFACTOR:
CC       Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC         Evidence={ECO:0000250|UniProtKB:P43534};
CC   -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis.
CC       {ECO:0000305|PubMed:7711083}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P43534}.
CC   -!- INDUCTION: Repressed by thiamine. {ECO:0000269|PubMed:7711083}.
CC   -!- SIMILARITY: Belongs to the NMT1/THI5 family. {ECO:0000305}.
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DR   EMBL; U15196; AAA70083.1; -; mRNA.
DR   PIR; S53697; S53697.
DR   AlphaFoldDB; P42882; -.
DR   SMR; P42882; -.
DR   PRIDE; P42882; -.
DR   UniPathway; UPA00060; -.
DR   GO; GO:0106344; F:4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase activity from histidine and PLP; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0009228; P:thiamine biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0009229; P:thiamine diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR   InterPro; IPR027939; NMT1/THI5.
DR   InterPro; IPR015168; SsuA/THI5.
DR   PANTHER; PTHR31528; PTHR31528; 1.
DR   Pfam; PF09084; NMT1; 1.
PE   2: Evidence at transcript level;
KW   Iron; Metal-binding; Pyridoxal phosphate; Thiamine biosynthesis;
KW   Transferase.
FT   CHAIN           1..342
FT                   /note="4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate
FT                   synthase"
FT                   /id="PRO_0000211622"
FT   MOTIF           195..199
FT                   /note="CCCFC; essential for catalytic activity, may be the
FT                   site of iron coordination"
FT                   /evidence="ECO:0000250|UniProtKB:P43534"
FT   ACT_SITE        66
FT                   /evidence="ECO:0000250|UniProtKB:P43534"
FT   BINDING         115..118
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000250|UniProtKB:P43534"
FT   MOD_RES         62
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT                   /evidence="ECO:0000250|UniProtKB:P43534"
SQ   SEQUENCE   342 AA;  38198 MW;  DD747AFFFF0A33CE CRC64;
     MSTDKITFLT NWHATPYHAP LYLAQSKGYF KEEGLKVALL EPNDPSDVTE IIGSGKVDMG
     FKAMIHTLAA KARNFPVTSI GSLLDEPFTG VVYLKDSGIT EDFRSLKGKK IGYVGEFGKI
     QIDELTKYYG MTADDYTAVR CGMNVTKAII RGDIDAGIGL ENVQMVELAE WLASQNRPRD
     DVQIVRIDQL AELGCCCFCS ILYIANDAFL AANPEKVQKF MRAVKRATDY VLAEPAAAFE
     EYVDMKPIMG TPVNRKIFER SFAYFSRDLK NVSRDWAKVT NYGKRLGILD ADFQPNYTNQ
     YLSWTLDADS TDPLGDQKRM AELQKEVACE GGFKRLQVAS SA