THI4_YEAST
ID THI4_YEAST Reviewed; 326 AA.
AC P32318; D6VUS4;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Thiamine thiazole synthase {ECO:0000255|HAMAP-Rule:MF_03158};
DE EC=2.4.2.60 {ECO:0000255|HAMAP-Rule:MF_03158, ECO:0000269|PubMed:22031445};
DE AltName: Full=Thiazole biosynthetic enzyme {ECO:0000255|HAMAP-Rule:MF_03158};
GN Name=THI4 {ECO:0000255|HAMAP-Rule:MF_03158}; Synonyms=ESP35, MOL1;
GN OrderedLocusNames=YGR144W; ORFNames=G6620;
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].
RX PubMed=1441749; DOI=10.1002/yea.320080903;
RA Praekelt U.M., Meacock P.A.;
RT "MOL1, a Saccharomyces cerevisiae gene that is highly expressed in early
RT stationary phase during growth on molasses.";
RL Yeast 8:699-710(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169869;
RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL Nature 387:81-84(1997).
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 PROTEIN SEQUENCE OF 3-10 AND 12-16, FUNCTION, SUBCELLULAR LOCATION, AND
RP INDUCTION.
RX PubMed=15544818; DOI=10.1016/j.jmb.2004.09.097;
RA Faou P., Tropschug M.;
RT "Neurospora crassa CyPBP37: a cytosolic stress protein that is able to
RT replace yeast Thi4p function in the synthesis of vitamin B1.";
RL J. Mol. Biol. 344:1147-1157(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 205-326.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8585325; DOI=10.1002/yea.320111410;
RA Skala J., Nawrocki A., Goffeau A.;
RT "The sequence of a 27 kb segment on the right arm of chromosome VII from
RT Saccharomyces cerevisiae reveals MOL1, NAT2, RPL30B, RSR1, CYS4, PEM1/CHO2,
RT NSR1 genes and ten new open reading frames.";
RL Yeast 11:1421-1427(1995).
RN [6]
RP THIAMINE REGULATION.
RX PubMed=7941734; DOI=10.1002/yea.320100407;
RA Praekelt U.M., Byrne K.L., Meacock P.A.;
RT "Regulation of THI4 (MOL1), a thiamine-biosynthetic gene of Saccharomyces
RT cerevisiae.";
RL Yeast 10:481-490(1994).
RN [7]
RP FUNCTION IN DNA DAMAGE TOLERANCE.
RX PubMed=9367751; DOI=10.1006/jmbi.1997.1302;
RA Machado C.R., Praekelt U.M., de Oliveira R.C., Barbosa A.C., Byrne K.L.,
RA Meacock P.A., Menck C.F.;
RT "Dual role for the yeast THI4 gene in thiamine biosynthesis and DNA damage
RT tolerance.";
RL J. Mol. Biol. 273:114-121(1997).
RN [8]
RP FUNCTION.
RX PubMed=16734458; DOI=10.1021/ja061413o;
RA Chatterjee A., Jurgenson C.T., Schroeder F.C., Ealick S.E., Begley T.P.;
RT "Thiamin biosynthesis in eukaryotes: characterization of the enzyme-bound
RT product of thiazole synthase from Saccharomyces cerevisiae and its
RT implications in thiazole biosynthesis.";
RL J. Am. Chem. Soc. 128:7158-7159(2006).
RN [9]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=16850348; DOI=10.1007/s00438-006-0130-z;
RA Mojzita D., Hohmann S.;
RT "Pdc2 coordinates expression of the THI regulon in the yeast Saccharomyces
RT cerevisiae.";
RL Mol. Genet. Genomics 276:147-161(2006).
RN [10]
RP FUNCTION IN STRESS TOLERANCE.
RX PubMed=16171982; DOI=10.1016/j.resmic.2005.07.004;
RA Medina-Silva R., Barros M.P., Galhardo R.S., Netto L.E., Colepicolo P.,
RA Menck C.F.;
RT "Heat stress promotes mitochondrial instability and oxidative responses in
RT yeast deficient in thiazole biosynthesis.";
RL Res. Microbiol. 157:275-281(2006).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF GLU-97; HIS-200; CYS-204; CYS-205; ASP-207;
RP HIS-237; ASP-238; ARG-301 AND PRO-304.
RX PubMed=17309261; DOI=10.1021/ja067606t;
RA Chatterjee A., Jurgenson C.T., Schroeder F.C., Ealick S.E., Begley T.P.;
RT "Biosynthesis of thiamin thiazole in eukaryotes: conversion of NAD to an
RT advanced intermediate.";
RL J. Am. Chem. Soc. 129:2914-2922(2007).
RN [12]
RP FUNCTION.
RX PubMed=18652458; DOI=10.1021/ja802140a;
RA Chatterjee A., Schroeder F.C., Jurgenson C.T., Ealick S.E., Begley T.P.;
RT "Biosynthesis of the thiamin-thiazole in eukaryotes: identification of a
RT thiazole tautomer intermediate.";
RL J. Am. Chem. Soc. 130:11394-11398(2008).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) IN COMPLEX WITH ADT, AND SUBUNIT.
RX PubMed=16964967; DOI=10.1021/bi061025z;
RA Jurgenson C.T., Chatterjee A., Begley T.P., Ealick S.E.;
RT "Structural insights into the function of the thiamin biosynthetic enzyme
RT Thi4 from Saccharomyces cerevisiae.";
RL Biochemistry 45:11061-11070(2006).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS), IRON-BINDING, FUNCTION, CATALYTIC
RP ACTIVITY, AND DIDEHYDROALANINE FORMATION AT CYS-205.
RX PubMed=22031445; DOI=10.1038/nature10503;
RA Chatterjee A., Abeydeera N.D., Bale S., Pai P.J., Dorrestein P.C.,
RA Russell D.H., Ealick S.E., Begley T.P.;
RT "Saccharomyces cerevisiae THI4p is a suicide thiamine thiazole synthase.";
RL Nature 478:542-546(2011).
CC -!- FUNCTION: Involved in biosynthesis of the thiamine precursor thiazole.
CC Catalyzes the conversion of NAD and glycine to adenosine diphosphate 5-
CC (2-hydroxyethyl)-4-methylthiazole-2-carboxylic acid (ADT), an
CC adenylated thiazole intermediate. The reaction includes an iron-
CC dependent sulfide transfer from a conserved cysteine residue of the
CC protein to a thiazole intermediate. The enzyme can only undergo a
CC single turnover, which suggests it is a suicide enzyme. May have
CC additional roles in adaptation to various stress conditions and in DNA
CC damage tolerance. {ECO:0000255|HAMAP-Rule:MF_03158,
CC ECO:0000269|PubMed:15544818, ECO:0000269|PubMed:16171982,
CC ECO:0000269|PubMed:16734458, ECO:0000269|PubMed:17309261,
CC ECO:0000269|PubMed:18652458, ECO:0000269|PubMed:22031445,
CC ECO:0000269|PubMed:9367751}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[ADP-thiazole synthase]-L-cysteine + glycine + NAD(+) = [ADP-
CC thiazole synthase]-dehydroalanine + ADP-5-ethyl-4-methylthiazole-2-
CC carboxylate + 2 H(+) + 3 H2O + nicotinamide; Xref=Rhea:RHEA:55708,
CC Rhea:RHEA-COMP:14264, Rhea:RHEA-COMP:14265, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:57540, ChEBI:CHEBI:90873,
CC ChEBI:CHEBI:139151; EC=2.4.2.60; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03158, ECO:0000269|PubMed:22031445};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:22031445};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000269|PubMed:22031445};
CC -!- SUBUNIT: Homooctamer; tetramer of dimers.
CC {ECO:0000269|PubMed:16964967}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15544818,
CC ECO:0000269|PubMed:16850348}. Nucleus {ECO:0000269|PubMed:16850348}.
CC Note=Excluded from the vacuole. {ECO:0000269|PubMed:16850348}.
CC -!- INDUCTION: Repressed by thiamine. {ECO:0000269|PubMed:15544818,
CC ECO:0000269|PubMed:16850348}.
CC -!- PTM: During the catalytic reaction, a sulfide is transferred from Cys-
CC 205 to a reaction intermediate, generating a dehydroalanine residue.
CC {ECO:0000269|PubMed:22031445}.
CC -!- MISCELLANEOUS: Expressed at high levels in the early stationary phase
CC of batch cultures growing on molasses, an industrial medium.
CC -!- SIMILARITY: Belongs to the THI4 family. {ECO:0000255|HAMAP-
CC Rule:MF_03158}.
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DR EMBL; X61669; CAA43843.1; -; Genomic_DNA.
DR EMBL; Z72929; CAA97157.1; -; Genomic_DNA.
DR EMBL; Z72930; CAA97159.1; -; Genomic_DNA.
DR EMBL; X85807; CAA59802.1; -; Genomic_DNA.
DR EMBL; BK006941; DAA08235.1; -; Genomic_DNA.
DR PIR; S25321; S25321.
DR RefSeq; NP_011660.1; NM_001181273.1.
DR PDB; 3FPZ; X-ray; 1.82 A; A/B=1-326.
DR PDB; 4Y4L; X-ray; 2.00 A; A/B/C/D=1-326.
DR PDBsum; 3FPZ; -.
DR PDBsum; 4Y4L; -.
DR AlphaFoldDB; P32318; -.
DR SMR; P32318; -.
DR BioGRID; 33392; 86.
DR DIP; DIP-1703N; -.
DR IntAct; P32318; 5.
DR MINT; P32318; -.
DR STRING; 4932.YGR144W; -.
DR PaxDb; P32318; -.
DR PRIDE; P32318; -.
DR EnsemblFungi; YGR144W_mRNA; YGR144W; YGR144W.
DR GeneID; 853047; -.
DR KEGG; sce:YGR144W; -.
DR SGD; S000003376; THI4.
DR VEuPathDB; FungiDB:YGR144W; -.
DR eggNOG; KOG2960; Eukaryota.
DR HOGENOM; CLU_053727_0_0_1; -.
DR InParanoid; P32318; -.
DR OMA; MWGGGMM; -.
DR BioCyc; MetaCyc:MON3O-153; -.
DR BioCyc; YEAST:MON3O-153; -.
DR BRENDA; 2.4.2.60; 984.
DR BRENDA; 2.8.1.10; 984.
DR EvolutionaryTrace; P32318; -.
DR PRO; PR:P32318; -.
DR Proteomes; UP000002311; Chromosome VII.
DR RNAct; P32318; protein.
DR GO; GO:0005829; C:cytosol; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0008198; F:ferrous iron binding; IDA:SGD.
DR GO; GO:0016763; F:pentosyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0000002; P:mitochondrial genome maintenance; IMP:SGD.
DR GO; GO:0009228; P:thiamine biosynthetic process; IMP:SGD.
DR GO; GO:0052837; P:thiazole biosynthetic process; IDA:SGD.
DR Gene3D; 3.50.50.60; -; 1.
DR HAMAP; MF_03158; THI4; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR027495; Sti35.
DR InterPro; IPR002922; Thi4_fam.
DR SUPFAM; SSF51905; SSF51905; 1.
DR TIGRFAMs; TIGR00292; TIGR00292; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Iron; Metal-binding;
KW NAD; Nucleus; Reference proteome; Thiamine biosynthesis; Transferase.
FT CHAIN 1..326
FT /note="Thiamine thiazole synthase"
FT /id="PRO_0000034058"
FT BINDING 76
FT /ligand="substrate"
FT BINDING 97..98
FT /ligand="substrate"
FT BINDING 105
FT /ligand="substrate"
FT BINDING 170
FT /ligand="substrate"
FT BINDING 207
FT /ligand="substrate"
FT BINDING 237
FT /ligand="substrate"
FT BINDING 291
FT /ligand="substrate"
FT BINDING 301..303
FT /ligand="substrate"
FT MOD_RES 205
FT /note="2,3-didehydroalanine (Cys)"
FT /evidence="ECO:0000269|PubMed:22031445"
FT MUTAGEN 97
FT /note="E->A,Q: No activity."
FT /evidence="ECO:0000269|PubMed:17309261"
FT MUTAGEN 200
FT /note="H->N: Partially active, trapping the enzyme at an
FT advanced intermediate, just before the sulfide transfer
FT reaction."
FT /evidence="ECO:0000269|PubMed:17309261"
FT MUTAGEN 204
FT /note="C->A: Partially active, trapping the enzyme at an
FT advanced intermediate, just before the sulfide transfer
FT reaction."
FT /evidence="ECO:0000269|PubMed:17309261"
FT MUTAGEN 205
FT /note="C->S: Partially active, with very weak activity
FT toward NAD."
FT /evidence="ECO:0000269|PubMed:17309261"
FT MUTAGEN 207
FT /note="D->A: No activity."
FT /evidence="ECO:0000269|PubMed:17309261"
FT MUTAGEN 237
FT /note="H->A,N: No activity."
FT /evidence="ECO:0000269|PubMed:17309261"
FT MUTAGEN 238
FT /note="D->A: Partially active, with very weak activity
FT toward NAD."
FT /evidence="ECO:0000269|PubMed:17309261"
FT MUTAGEN 301
FT /note="R->A,Q: No activity."
FT /evidence="ECO:0000269|PubMed:17309261"
FT MUTAGEN 304
FT /note="P->A: No activity."
FT /evidence="ECO:0000269|PubMed:17309261"
FT HELIX 17..19
FT /evidence="ECO:0007829|PDB:3FPZ"
FT TURN 25..29
FT /evidence="ECO:0007829|PDB:3FPZ"
FT HELIX 45..62
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 65..71
FT /evidence="ECO:0007829|PDB:3FPZ"
FT HELIX 75..87
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:3FPZ"
FT TURN 104..107
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:3FPZ"
FT TURN 120..122
FT /evidence="ECO:0007829|PDB:3FPZ"
FT HELIX 123..128
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 137..143
FT /evidence="ECO:0007829|PDB:3FPZ"
FT HELIX 145..157
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 162..165
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 168..178
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 180..183
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 185..193
FT /evidence="ECO:0007829|PDB:3FPZ"
FT HELIX 194..197
FT /evidence="ECO:0007829|PDB:3FPZ"
FT TURN 198..201
FT /evidence="ECO:0007829|PDB:4Y4L"
FT STRAND 209..214
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:3FPZ"
FT HELIX 244..252
FT /evidence="ECO:0007829|PDB:3FPZ"
FT HELIX 266..276
FT /evidence="ECO:0007829|PDB:3FPZ"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:3FPZ"
FT HELIX 291..297
FT /evidence="ECO:0007829|PDB:3FPZ"
FT HELIX 307..325
FT /evidence="ECO:0007829|PDB:3FPZ"
SQ SEQUENCE 326 AA; 34991 MW; 843790F2CE00BF02 CRC64;
MSATSTATST SASQLHLNST PVTHCLSDIV KKEDWSDFKF APIRESTVSR AMTSRYFKDL
DKFAVSDVII VGAGSSGLSA AYVIAKNRPD LKVCIIESSV APGGGSWLGG QLFSAMVMRK
PAHLFLQELE IPYEDEGDYV VVKHAALFIS TVLSKVLQLP NVKLFNATCV EDLVTRPPTE
KGEVTVAGVV TNWTLVTQAH GTQCCMDPNV IELAGYKNDG TRDLSQKHGV ILSTTGHDGP
FGAFCAKRIV DIDQNQKLGG MKGLDMNHAE HDVVIHSGAY AGVDNMYFAG MEVAELDGLN
RMGPTFGAMA LSGVHAAEQI LKHFAA
