THI4_NEUCR
ID THI4_NEUCR Reviewed; 344 AA.
AC Q1K6I4; Q9HGR2; V5IKI8;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Thiamine thiazole synthase {ECO:0000255|HAMAP-Rule:MF_03158};
DE EC=2.4.2.60 {ECO:0000255|HAMAP-Rule:MF_03158};
DE AltName: Full=37 kDa NcCyP41-binding protein;
DE Short=CyPBP37;
DE AltName: Full=Thiazole biosynthetic enzyme {ECO:0000255|HAMAP-Rule:MF_03158};
GN ORFNames=NCU06110;
OS Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS FGSC 987).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX NCBI_TaxID=367110;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 5-16; 22-34; 158-169;
RP 178-191; 260-265 AND 326-338, AND INTERACTION WITH CYP-41.
RC STRAIN=74A;
RX PubMed=14568539; DOI=10.1016/j.jmb.2003.09.003;
RA Faou P., Tropschug M.;
RT "A novel binding protein for a member of CyP40-type Cyclophilins: N.crassa
RT CyPBP37, a growth and thiamine regulated protein homolog to yeast Thi4p.";
RL J. Mol. Biol. 333:831-844(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=12712197; DOI=10.1038/nature01554;
RA Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT "The genome sequence of the filamentous fungus Neurospora crassa.";
RL Nature 422:859-868(2003).
RN [3]
RP PROTEIN SEQUENCE OF 2-8, FUNCTION, SUBCELLULAR LOCATION, AND 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 [4]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH ADT, AND
RP IRON-BINDING.
RA Kang Y.N., Bale S., Begley T.P., Ealick S.E.;
RT "Crystal structure of thiazole synthase Thi4 from Neurospora crassa.";
RL Submitted (SEP-2009) to the PDB data bank.
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}.
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};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03158};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000255|HAMAP-Rule:MF_03158};
CC -!- SUBUNIT: Homooctamer (By similarity). Interacts with cyp-41.
CC {ECO:0000255|HAMAP-Rule:MF_03158, ECO:0000269|PubMed:14568539,
CC ECO:0000269|Ref.4}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03158}.
CC Nucleus {ECO:0000255|HAMAP-Rule:MF_03158}.
CC -!- INDUCTION: Repressed by thiamine, but not by thiazole. Induced by
CC various stress conditions, including heat, cold or osmotic shock.
CC {ECO:0000269|PubMed:15544818}.
CC -!- PTM: During the catalytic reaction, a sulfide is transferred from Cys-
CC 232 to a reaction intermediate, generating a dehydroalanine residue.
CC {ECO:0000255|HAMAP-Rule:MF_03158}.
CC -!- SIMILARITY: Belongs to the THI4 family. {ECO:0000255|HAMAP-
CC Rule:MF_03158}.
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DR EMBL; AJ297565; CAC03570.1; -; mRNA.
DR EMBL; CM002242; ESA41902.1; -; Genomic_DNA.
DR EMBL; CM002242; ESA41903.1; -; Genomic_DNA.
DR EMBL; CM002242; ESA41904.1; -; Genomic_DNA.
DR EMBL; CM002242; ESA41905.1; -; Genomic_DNA.
DR RefSeq; XP_011395239.1; XM_011396937.1.
DR RefSeq; XP_011395240.1; XM_011396938.1.
DR RefSeq; XP_011395241.1; XM_011396939.1.
DR RefSeq; XP_011395242.1; XM_011396940.1.
DR PDB; 3JSK; X-ray; 2.70 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-344.
DR PDBsum; 3JSK; -.
DR AlphaFoldDB; Q1K6I4; -.
DR SMR; Q1K6I4; -.
DR STRING; 5141.EFNCRP00000005451; -.
DR PRIDE; Q1K6I4; -.
DR EnsemblFungi; ESA41902; ESA41902; NCU06110.
DR EnsemblFungi; ESA41903; ESA41903; NCU06110.
DR EnsemblFungi; ESA41904; ESA41904; NCU06110.
DR EnsemblFungi; ESA41905; ESA41905; NCU06110.
DR GeneID; 3876110; -.
DR KEGG; ncr:NCU06110; -.
DR VEuPathDB; FungiDB:NCU06110; -.
DR HOGENOM; CLU_053727_0_0_1; -.
DR InParanoid; Q1K6I4; -.
DR OMA; MWGGGMM; -.
DR BRENDA; 2.4.2.60; 3627.
DR Proteomes; UP000001805; Chromosome 7, Linkage Group VII.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-UniRule.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005506; F:iron ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0016763; F:pentosyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0009228; P:thiamine biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0052837; P:thiazole biosynthetic process; IEA:UniProtKB-UniRule.
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..344
FT /note="Thiamine thiazole synthase"
FT /id="PRO_0000415877"
FT BINDING 90
FT /ligand="substrate"
FT BINDING 111..112
FT /ligand="substrate"
FT BINDING 119
FT /ligand="substrate"
FT BINDING 184
FT /ligand="substrate"
FT BINDING 234
FT /ligand="substrate"
FT BINDING 249
FT /ligand="substrate"
FT BINDING 301
FT /ligand="substrate"
FT BINDING 311..313
FT /ligand="substrate"
FT MOD_RES 232
FT /note="2,3-didehydroalanine (Cys)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03158"
FT CONFLICT 31
FT /note="R -> RV (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 38..43
FT /evidence="ECO:0007829|PDB:3JSK"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:3JSK"
FT HELIX 59..78
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:3JSK"
FT HELIX 89..101
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 107..115
FT /evidence="ECO:0007829|PDB:3JSK"
FT TURN 118..121
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:3JSK"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:3JSK"
FT HELIX 137..143
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 151..157
FT /evidence="ECO:0007829|PDB:3JSK"
FT HELIX 159..171
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 182..191
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 211..220
FT /evidence="ECO:0007829|PDB:3JSK"
FT HELIX 221..224
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 236..239
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 249..254
FT /evidence="ECO:0007829|PDB:3JSK"
FT HELIX 256..263
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:3JSK"
FT HELIX 278..287
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 290..293
FT /evidence="ECO:0007829|PDB:3JSK"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:3JSK"
FT HELIX 300..302
FT /evidence="ECO:0007829|PDB:3JSK"
FT HELIX 303..307
FT /evidence="ECO:0007829|PDB:3JSK"
FT HELIX 317..341
FT /evidence="ECO:0007829|PDB:3JSK"
SQ SEQUENCE 344 AA; 36864 MW; AF9721DCEB155E64 CRC64;
MSPSVLEPQS VPTLVNVGLK AVGRNDAPVE RDARGLSKPL LELMPTLGTD AFTFSPIRES
TVSRAMTRRY FADLDAHAET DIVIVGAGSC GLSAAYVLST LRPDLRITIV EAGVAPGGGA
WLGGQLFSAM VMRKPADVFL DEVGVPYEDE GDYVVVKHAA LFTSTVLSKV LQRPNVKLFN
ATTVEDLITR KHHAESSSSS DDGEAEDEAK VRIAGVVTNW TLVSMHHDDQ SCMDPNTINA
PVIISTTGHD GPFGAFSVKR LVSMKQMERL NGMRGLDMQS AEDAIVNNTR EIVPGLIVGG
MELSEIDGAN RMGPTFGAMA LSGVKAAHEA IRVFDLRKAQ NDKC
