THI5_CANAW
ID THI5_CANAW Reviewed; 339 AA.
AC C4YMW2;
DT 07-JAN-2015, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 1.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase {ECO:0000250|UniProtKB:P43534};
DE Short=HMP-P synthase {ECO:0000305};
DE Short=Hydroxymethylpyrimidine phosphate synthase {ECO:0000305};
DE EC=2.-.-.- {ECO:0000269|PubMed:22568620};
DE AltName: Full=Thiamine biosynthesis protein 5 {ECO:0000303|PubMed:22568620};
DE AltName: Full=Thiamine pyrimidine synthase {ECO:0000303|PubMed:22568620};
GN Name=THI5 {ECO:0000303|PubMed:22568620}; ORFNames=CAWG_02199;
OS Candida albicans (strain WO-1) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=294748;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=WO-1;
RX PubMed=19465905; DOI=10.1038/nature08064;
RA Butler G., Rasmussen M.D., Lin M.F., Santos M.A.S., Sakthikumar S.,
RA Munro C.A., Rheinbay E., Grabherr M., Forche A., Reedy J.L., Agrafioti I.,
RA Arnaud M.B., Bates S., Brown A.J.P., Brunke S., Costanzo M.C.,
RA Fitzpatrick D.A., de Groot P.W.J., Harris D., Hoyer L.L., Hube B.,
RA Klis F.M., Kodira C., Lennard N., Logue M.E., Martin R., Neiman A.M.,
RA Nikolaou E., Quail M.A., Quinn J., Santos M.C., Schmitzberger F.F.,
RA Sherlock G., Shah P., Silverstein K.A.T., Skrzypek M.S., Soll D.,
RA Staggs R., Stansfield I., Stumpf M.P.H., Sudbery P.E., Srikantha T.,
RA Zeng Q., Berman J., Berriman M., Heitman J., Gow N.A.R., Lorenz M.C.,
RA Birren B.W., Kellis M., Cuomo C.A.;
RT "Evolution of pathogenicity and sexual reproduction in eight Candida
RT genomes.";
RL Nature 459:657-662(2009).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF WILD-TYPE IN COMPLEX WITH
RP PYRIDOXAL PHOSPHATE AND OF MUTANT GLY-66, FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, SUBUNIT, MASS SPECTROMETRY, ACTIVE SITE, AND MUTAGENESIS OF
RP HIS-66.
RX PubMed=22568620; DOI=10.1021/ja302474a;
RA Lai R.Y., Huang S., Fenwick M.K., Hazra A., Zhang Y., Rajashankar K.,
RA Philmus B., Kinsland C., Sanders J.M., Ealick S.E., Begley T.P.;
RT "Thiamin pyrimidine biosynthesis in Candida albicans: a remarkable reaction
RT between histidine and pyridoxal phosphate.";
RL J. Am. Chem. Soc. 134:9157-9159(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:22568620}.
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:22568620};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65757;
CC Evidence={ECO:0000269|PubMed:22568620};
CC -!- COFACTOR:
CC Name=Fe(3+); Xref=ChEBI:CHEBI:29034;
CC Evidence={ECO:0000269|PubMed:22568620};
CC -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis.
CC {ECO:0000305|PubMed:22568620}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:22568620}.
CC -!- MASS SPECTROMETRY: Mass=40408; Method=Electrospray; Note=The measured
CC mass includes the mass of an N-terminal poly-histidine tag, expressed
CC in E.coli.; Evidence={ECO:0000269|PubMed:22568620};
CC -!- SIMILARITY: Belongs to the NMT1/THI5 family. {ECO:0000305}.
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DR EMBL; CM000309; EEQ43943.1; -; Genomic_DNA.
DR PDB; 4ESW; X-ray; 1.60 A; A/B=1-339.
DR PDB; 4ESX; X-ray; 2.20 A; A/B=1-339.
DR PDBsum; 4ESW; -.
DR PDBsum; 4ESX; -.
DR AlphaFoldDB; C4YMW2; -.
DR SMR; C4YMW2; -.
DR STRING; 5476.C4YMW2; -.
DR PRIDE; C4YMW2; -.
DR EnsemblFungi; EEQ43943; EEQ43943; CAWG_02199.
DR VEuPathDB; FungiDB:CAWG_02199; -.
DR HOGENOM; CLU_028871_6_3_1; -.
DR OMA; DWFVNPD; -.
DR UniPathway; UPA00060; -.
DR Proteomes; UP000001429; Chromosome R.
DR GO; GO:0106344; F:4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase activity from histidine and PLP; IDA: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 1: Evidence at protein level;
KW 3D-structure; Iron; Metal-binding; Pyridoxal phosphate;
KW Thiamine biosynthesis; Transferase.
FT CHAIN 1..339
FT /note="4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate
FT synthase"
FT /id="PRO_0000431581"
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:0000305|PubMed:22568620"
FT BINDING 115..118
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:22568620"
FT MOD_RES 62
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:22568620"
FT MUTAGEN 66
FT /note="H->N,G: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:22568620"
FT STRAND 5..9
FT /evidence="ECO:0007829|PDB:4ESW"
FT STRAND 11..14
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 16..18
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 19..26
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 29..32
FT /evidence="ECO:0007829|PDB:4ESW"
FT STRAND 36..44
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 48..53
FT /evidence="ECO:0007829|PDB:4ESW"
FT STRAND 56..63
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 64..72
FT /evidence="ECO:0007829|PDB:4ESW"
FT STRAND 77..84
FT /evidence="ECO:0007829|PDB:4ESW"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:4ESW"
FT STRAND 110..116
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 117..126
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:4ESW"
FT STRAND 136..140
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 145..150
FT /evidence="ECO:0007829|PDB:4ESW"
FT STRAND 153..160
FT /evidence="ECO:0007829|PDB:4ESW"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 164..174
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:4ESW"
FT STRAND 182..186
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 187..190
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 197..199
FT /evidence="ECO:0007829|PDB:4ESW"
FT STRAND 201..206
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 207..212
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 214..233
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 235..245
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 247..250
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 252..262
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 273..285
FT /evidence="ECO:0007829|PDB:4ESW"
FT HELIX 313..330
FT /evidence="ECO:0007829|PDB:4ESW"
SQ SEQUENCE 339 AA; 38377 MW; A9E0369CC337659F CRC64;
MSTNKITFLL NWEAAPYHIP VYLANIKGYF KDENLDIAIL EPSNPSDVTE LVGSGKVDMG
LKAMVHTLAA KARGFPVTSI GSLLDEPFTG ICYLEGSGIT SDFQSLKGKR IGYVGEFGKI
QVDELTKHYG MTPDDYVAVR CGMNVAKYIL EGTIDCGIGI ECIQQVELEE ALKEQGKDSN
DAKMLRIDKL AELGCCCFCT ILYIANDKFI AENPQAVKKF LKAIKRATDY MLAHPREAWA
EYGNFKPTMQ TDLNTKKFQR CYAYFSESLY NVHRDWRKVN NYGKRLDILP ENYVPNYTNE
YLSWPEPKEV DDPEKAQDLM LKHQEECKTC GGYKRLVLA
