THI5_LEGPH
ID THI5_LEGPH Reviewed; 316 AA.
AC Q5ZV75;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase {ECO:0000303|PubMed:33034117};
DE Short=HMP-P synthase {ECO:0000303|PubMed:33034117};
DE Short=Hydroxymethylpyrimidine phosphate synthase {ECO:0000305};
DE EC=2.-.-.- {ECO:0000269|PubMed:33034117};
DE AltName: Full=Thiamine biosynthesis protein 5 {ECO:0000250|UniProtKB:P43534};
DE AltName: Full=Thiamine pyrimidine synthase {ECO:0000250|UniProtKB:C4YMW2};
GN Name=thi5 {ECO:0000303|PubMed:33034117};
GN Synonyms=nmt1 {ECO:0000312|EMBL:AAU27647.1},
GN thi3 {ECO:0000312|EMBL:AAU27647.1};
GN OrderedLocusNames=lpg1565 {ECO:0000312|EMBL:AAU27647.1};
OS Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC
OS 33152 / DSM 7513).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales;
OC Legionellaceae; Legionella.
OX NCBI_TaxID=272624 {ECO:0000312|Proteomes:UP000000609};
RN [1] {ECO:0000312|Proteomes:UP000000609}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513
RC {ECO:0000312|Proteomes:UP000000609};
RX PubMed=15448271; DOI=10.1126/science.1099776;
RA Chien M., Morozova I., Shi S., Sheng H., Chen J., Gomez S.M., Asamani G.,
RA Hill K., Nuara J., Feder M., Rineer J., Greenberg J.J., Steshenko V.,
RA Park S.H., Zhao B., Teplitskaya E., Edwards J.R., Pampou S., Georghiou A.,
RA Chou I.-C., Iannuccilli W., Ulz M.E., Kim D.H., Geringer-Sameth A.,
RA Goldsberry C., Morozov P., Fischer S.G., Segal G., Qu X., Rzhetsky A.,
RA Zhang P., Cayanis E., De Jong P.J., Ju J., Kalachikov S., Shuman H.A.,
RA Russo J.J.;
RT "The genomic sequence of the accidental pathogen Legionella pneumophila.";
RL Science 305:1966-1968(2004).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY, SUBUNIT, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF HIS-70; GLY-118; GLU-119 AND PHE-120.
RX PubMed=33034117; DOI=10.1111/mmi.14622;
RA Paxhia M.D., Swanson M.S., Downs D.M.;
RT "Functional characterization of the HMP-P synthase of Legionella
RT pneumophila (Lpg1565).";
RL Mol. Microbiol. 115:539-553(2021).
CC -!- FUNCTION: Responsible for the formation of the pyrimidine heterocycle
CC in the thiamine biosynthesis pathway (PubMed:33034117). Catalyzes the
CC formation of hydroxymethylpyrimidine phosphate (HMP-P) from histidine
CC and pyridoxal phosphate (PLP) (Probable). The protein uses PLP and the
CC active site histidine to form HMP-P, generating an inactive enzyme (By
CC similarity). The enzyme can only undergo a single turnover, which
CC suggests it is a suicide enzyme (By similarity).
CC {ECO:0000250|UniProtKB:P43534, ECO:0000269|PubMed:33034117,
CC ECO:0000305|PubMed:33034117}.
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:33034117};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65757;
CC Evidence={ECO:0000269|PubMed:33034117};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:33034117};
CC -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis.
CC {ECO:0000305|PubMed:33034117}.
CC -!- SUBUNIT: Homodimer. {ECO:0000305|PubMed:33034117}.
CC -!- DISRUPTION PHENOTYPE: Growth auxotrophic for thiamine; growth partially
CC restored by hydroxymethylpyrimidine (HMP).
CC {ECO:0000269|PubMed:33034117}.
CC -!- SIMILARITY: Belongs to the NMT1/THI5 family. {ECO:0000305}.
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DR EMBL; AE017354; AAU27647.1; -; Genomic_DNA.
DR RefSeq; YP_095594.1; NC_002942.5.
DR AlphaFoldDB; Q5ZV75; -.
DR SMR; Q5ZV75; -.
DR STRING; 272624.lpg1565; -.
DR PaxDb; Q5ZV75; -.
DR EnsemblBacteria; AAU27647; AAU27647; lpg1565.
DR KEGG; lpn:lpg1565; -.
DR PATRIC; fig|272624.6.peg.1639; -.
DR eggNOG; COG0715; Bacteria.
DR HOGENOM; CLU_028871_6_3_6; -.
DR OMA; YVMAMYQ; -.
DR UniPathway; UPA00060; -.
DR Proteomes; UP000000609; Chromosome.
DR GO; GO:0106344; F:4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase activity from histidine and PLP; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070279; F:vitamin B6 binding; IDA:UniProtKB.
DR GO; GO:0009228; P:thiamine biosynthetic process; IMP:UniProtKB.
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 1: Evidence at protein level;
KW Iron; Metal-binding; Pyridoxal phosphate; Reference proteome;
KW Thiamine biosynthesis; Transferase.
FT CHAIN 1..316
FT /note="4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate
FT synthase"
FT /id="PRO_0000452085"
FT MOTIF 191..195
FT /note="CCCFC; essential for catalytic activity, may be the
FT site of iron coordination"
FT /evidence="ECO:0000250|UniProtKB:P43534"
FT ACT_SITE 70
FT /evidence="ECO:0000250|UniProtKB:P43534"
FT BINDING 118..121
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P43534"
FT MOD_RES 66
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P43534"
FT MUTAGEN 70
FT /note="H->A: Decreases pyridoxal phosphate (PLP) binding."
FT /evidence="ECO:0000269|PubMed:33034117"
FT MUTAGEN 118
FT /note="G->A: Decreases catalytic activity."
FT /evidence="ECO:0000269|PubMed:33034117"
FT MUTAGEN 119
FT /note="E->A: Decreases catalytic activity."
FT /evidence="ECO:0000269|PubMed:33034117"
FT MUTAGEN 120
FT /note="F->A: Decreases catalytic activity."
FT /evidence="ECO:0000269|PubMed:33034117"
SQ SEQUENCE 316 AA; 35276 MW; 07A59B40553DA971 CRC64;
MAMSSLKSRV TLLLNWYTNP YHTPILVAQQ LGFYSEEDIK LAILEPADPS DVTEIVGLGT
VDFGVKAMIH TVAAKAKGYP VTSIGTLLDE PPTGLIALKS SGINSFQDIV GKRVGYIGEF
GKKIIDDLAS LAGIDPTSYK TVRIGMNVTD AIYRDVIDTG IGFINFQKVE LEHLCGETVF
LRIDQLAGLG CCCFCSIQFI VPEITLQQPE LVKGFLRATQ RGAAYTTEKP EEAYELLCQA
KPQLRTPLYQ KIFTRTLPFF SRTLINVDRD WDKVGRYTKH LKIIDEHFDI SQCYTNRFLP
DTPYSDLKPI ACCLEN
