THI4_HALVD
ID THI4_HALVD Reviewed; 307 AA.
AC D4GSS5; A0A384KZ83; L9UNI3;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Thiamine thiazole synthase {ECO:0000255|HAMAP-Rule:MF_00304, ECO:0000303|PubMed:25348237};
DE EC=2.4.2.60 {ECO:0000250|UniProtKB:P32318, ECO:0000255|HAMAP-Rule:MF_00304};
DE AltName: Full=Thiazole biosynthetic enzyme {ECO:0000305};
GN Name=thi4 {ECO:0000255|HAMAP-Rule:MF_00304, ECO:0000303|PubMed:25348237,
GN ECO:0000312|EMBL:ADE05087.1};
GN OrderedLocusNames=HVO_0665 {ECO:0000312|EMBL:ADE05087.1};
GN ORFNames=C498_15398 {ECO:0000312|EMBL:ELY26470.1};
OS Haloferax volcanii (strain ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 /
OS NCIMB 2012 / VKM B-1768 / DS2) (Halobacterium volcanii).
OC Archaea; Euryarchaeota; Stenosarchaea group; Halobacteria; Haloferacales;
OC Haloferacaceae; Haloferax.
OX NCBI_TaxID=309800 {ECO:0000312|EMBL:ADE05087.1};
RN [1] {ECO:0000312|EMBL:ADE05087.1, ECO:0000312|Proteomes:UP000008243}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 / NCIMB 2012 / VKM
RC B-1768 / DS2 {ECO:0000312|Proteomes:UP000008243};
RX PubMed=20333302; DOI=10.1371/journal.pone.0009605;
RA Hartman A.L., Norais C., Badger J.H., Delmas S., Haldenby S., Madupu R.,
RA Robinson J., Khouri H., Ren Q., Lowe T.M., Maupin-Furlow J.,
RA Pohlschroder M., Daniels C., Pfeiffer F., Allers T., Eisen J.A.;
RT "The complete genome sequence of Haloferax volcanii DS2, a model
RT archaeon.";
RL PLoS ONE 5:E9605-E9605(2010).
RN [2] {ECO:0000312|EMBL:ELY26470.1, ECO:0000312|Proteomes:UP000011532}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 / NCIMB 2012 / VKM
RC B-1768 / DS2 {ECO:0000312|Proteomes:UP000011532};
RX PubMed=25393412; DOI=10.1371/journal.pgen.1004784;
RA Becker E.A., Seitzer P.M., Tritt A., Larsen D., Krusor M., Yao A.I., Wu D.,
RA Madern D., Eisen J.A., Darling A.E., Facciotti M.T.;
RT "Phylogenetically driven sequencing of extremely halophilic archaea reveals
RT strategies for static and dynamic osmo-response.";
RL PLoS Genet. 10:E1004784-E1004784(2014).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF CYS-165, 3D-STRUCTURE
RP MODELING, AND PHYLOGENETIC ANALYSIS.
RC STRAIN=DS2 / DS70 {ECO:0000303|PubMed:25348237};
RX PubMed=25348237; DOI=10.1186/s12866-014-0260-0;
RA Hwang S., Cordova B., Chavarria N., Elbanna D., McHugh S., Rojas J.,
RA Pfeiffer F., Maupin-Furlow J.A.;
RT "Conserved active site cysteine residue of archaeal THI4 homolog is
RT essential for thiamine biosynthesis in Haloferax volcanii.";
RL BMC Microbiol. 14:260-260(2014).
CC -!- FUNCTION: Involved in biosynthesis of the thiamine precursor thiazole
CC (PubMed:25348237). Catalyzes the conversion of NAD and glycine to
CC adenosine diphosphate 5-(2-hydroxyethyl)-4-methylthiazole-2-carboxylic
CC acid (ADT), an adenylated thiazole intermediate. The reaction includes
CC an iron-dependent sulfide transfer from a conserved cysteine residue of
CC the protein to a thiazole intermediate. The enzyme can only undergo a
CC single turnover, which suggests it is a suicide enzyme (By similarity).
CC {ECO:0000255|HAMAP-Rule:MF_00304, ECO:0000269|PubMed:25348237}.
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;
CC Evidence={ECO:0000250|UniProtKB:P32318, ECO:0000255|HAMAP-
CC Rule:MF_00304};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00304};
CC -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_00304}.
CC -!- SUBUNIT: Homooctamer; tetramer of dimers. {ECO:0000255|HAMAP-
CC Rule:MF_00304}.
CC -!- PTM: During the catalytic reaction, a sulfide is transferred from Cys-
CC 165 to a reaction intermediate, generating a dehydroalanine residue.
CC {ECO:0000250|UniProtKB:P32318, ECO:0000255|HAMAP-Rule:MF_00304}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are auxotrophic for
CC thiamine. The mutants thiamine requirement can be overcome by adding
CC thiazole moiety 4-methyl-5-(beta-hydroxyethyl)thiazole (THZ) to the
CC growth medium. {ECO:0000269|PubMed:25348237}.
CC -!- SIMILARITY: Belongs to the THI4 family. {ECO:0000255|HAMAP-
CC Rule:MF_00304, ECO:0000305}.
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DR EMBL; CP001956; ADE05087.1; -; Genomic_DNA.
DR EMBL; AOHU01000097; ELY26470.1; -; Genomic_DNA.
DR RefSeq; WP_004044270.1; NZ_AOHU01000097.1.
DR STRING; 309800.C498_15398; -.
DR EnsemblBacteria; ADE05087; ADE05087; HVO_0665.
DR EnsemblBacteria; ELY26470; ELY26470; C498_15398.
DR GeneID; 8924004; -.
DR KEGG; hvo:HVO_0665; -.
DR PATRIC; fig|309800.29.peg.2977; -.
DR eggNOG; arCOG00574; Archaea.
DR HOGENOM; CLU_053727_2_0_2; -.
DR OMA; GIVMNWT; -.
DR OrthoDB; 61905at2157; -.
DR BioCyc; MetaCyc:MON-20828; -.
DR UniPathway; UPA00060; -.
DR Proteomes; UP000008243; Chromosome.
DR Proteomes; UP000011532; Unassembled WGS sequence.
DR GO; GO:0008198; F:ferrous iron binding; ISS:UniProtKB.
DR GO; GO:0016763; F:pentosyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0009228; P:thiamine biosynthetic process; IMP:UniProtKB.
DR GO; GO:0009229; P:thiamine diphosphate biosynthetic process; IMP:UniProtKB.
DR GO; GO:0052837; P:thiazole biosynthetic process; IMP:UniProtKB.
DR Gene3D; 3.50.50.60; -; 1.
DR HAMAP; MF_00304; Thi4; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR002922; Thi4_fam.
DR InterPro; IPR022828; Thi4_prok.
DR SUPFAM; SSF51905; SSF51905; 1.
DR TIGRFAMs; TIGR00292; TIGR00292; 1.
PE 1: Evidence at protein level;
KW Iron; Metal-binding; NAD; Reference proteome; Thiamine biosynthesis;
KW Transferase.
FT CHAIN 1..307
FT /note="Thiamine thiazole synthase"
FT /id="PRO_0000454766"
FT BINDING 42
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_note="ligand shared between two adjacent protomers"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00304"
FT BINDING 61..62
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_note="ligand shared between two adjacent protomers"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00304"
FT BINDING 69
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_note="ligand shared between two adjacent protomers"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00304"
FT BINDING 167
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="ligand shared between two adjacent protomers"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00304"
FT BINDING 167
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_note="ligand shared between two adjacent protomers"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00304"
FT BINDING 182
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="ligand shared between two adjacent protomers"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00304"
FT BINDING 257
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_note="ligand shared between two adjacent protomers"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00304"
FT BINDING 267
FT /ligand="glycine"
FT /ligand_id="ChEBI:CHEBI:57305"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00304"
FT MOD_RES 165
FT /note="2,3-didehydroalanine (Cys)"
FT /evidence="ECO:0000250|UniProtKB:P32318, ECO:0000255|HAMAP-
FT Rule:MF_00304"
FT MUTAGEN 165
FT /note="C->A: Not able to trans-complement the deletion
FT mutant of this gene."
FT /evidence="ECO:0000269|PubMed:25348237"
SQ SEQUENCE 307 AA; 32424 MW; 5A803FA06801153D CRC64;
MSFDGFTDAT EAQVTRAISD SWMEEFRERT DTEVIVVGGG PSGLVAAKEL AERGVDVTIV
EKNNYLGGGF WLGGFLMNKV TVRDPAQRVL DELGVPYEES DEAEGLYVAD GPHACSALIK
AACDAGAKIQ NMTEFTDVVL REDDRVGGIV MNWTPVHALP RELTCVDPIA VESDLVLDAT
GHDAVVLSKL SERGVLDVNG IEHAKEHNTG MDKTADGEYG APGHDSPGHD SMWVSESEDS
IVDATGVVHP GVVASGMAVA TAHHLPRMGP TFGAMLLSGR QAAQSCLDEL GRDAPDVSIS
GPAPADD
