THLA_CLOAB
ID THLA_CLOAB Reviewed; 392 AA.
AC P45359;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Acetyl-CoA acetyltransferase {ECO:0000303|PubMed:1685080};
DE EC=2.3.1.9 {ECO:0000269|PubMed:1685080, ECO:0000269|PubMed:26391388};
DE AltName: Full=Acetoacetyl-CoA thiolase;
DE AltName: Full=CaTHL {ECO:0000303|PubMed:26391388};
GN Name=thlA; Synonyms=thl; OrderedLocusNames=CA_C2873;
OS Clostridium acetobutylicum (strain ATCC 824 / DSM 792 / JCM 1419 / LMG 5710
OS / VKM B-1787).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=272562;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 824 / DSM 792 / JCM 1419 / LMG 5710 / VKM B-1787;
RX PubMed=7867955; DOI=10.1016/0378-1119(94)00838-j;
RA Stim-Herndon K.P., Petersen D.J., Bennett G.N.;
RT "Characterization of an acetyl-CoA C-acetyltransferase (thiolase) gene from
RT Clostridium acetobutylicum ATCC 824.";
RL Gene 154:81-85(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 824 / DSM 792 / JCM 1419 / LMG 5710 / VKM B-1787;
RX PubMed=11075929;
RA Winzer K., Lorenz K., Zickner B., Duerre P.;
RT "Differential regulation of two thiolase genes from Clostridium
RT acetobutylicum DSM 792.";
RL J. Mol. Microbiol. Biotechnol. 2:531-541(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 824 / DSM 792 / JCM 1419 / LMG 5710 / VKM B-1787;
RX PubMed=11466286; DOI=10.1128/jb.183.16.4823-4838.2001;
RA Noelling J., Breton G., Omelchenko M.V., Makarova K.S., Zeng Q., Gibson R.,
RA Lee H.M., Dubois J., Qiu D., Hitti J., Wolf Y.I., Tatusov R.L., Sabathe F.,
RA Doucette-Stamm L.A., Soucaille P., Daly M.J., Bennett G.N., Koonin E.V.,
RA Smith D.R.;
RT "Genome sequence and comparative analysis of the solvent-producing
RT bacterium Clostridium acetobutylicum.";
RL J. Bacteriol. 183:4823-4838(2001).
RN [4]
RP PROTEIN SEQUENCE OF 1-30, FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 824 / DSM 792 / JCM 1419 / LMG 5710 / VKM B-1787;
RX PubMed=1685080; DOI=10.1128/aem.57.9.2735-2741.1991;
RA Petersen D.J., Bennett G.N.;
RT "Cloning of the Clostridium acetobutylicum ATCC 824 acetyl coenzyme A
RT acetyltransferase (thiolase; EC 2.3.1.9) gene.";
RL Appl. Environ. Microbiol. 57:2735-2741(1991).
RN [5] {ECO:0007744|PDB:4WYR, ECO:0007744|PDB:4XL2}
RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF WILD-TYPE IN OXIDIZED FORM IN
RP COMPLEX WITH ACETATE AND OF MUTANT GLN-77/TYR-153/LYS-286, FUNCTION,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS OF
RP VAL-77; ASN-153 AND ALA-286.
RX PubMed=26391388; DOI=10.1038/ncomms9410;
RA Kim S., Jang Y.S., Ha S.C., Ahn J.W., Kim E.J., Lim J.H., Cho C., Ryu Y.S.,
RA Lee S.K., Lee S.Y., Kim K.J.;
RT "Redox-switch regulatory mechanism of thiolase from Clostridium
RT acetobutylicum.";
RL Nat. Commun. 6:8410-8410(2015).
CC -!- FUNCTION: Catalyzes the condensation of two molecules of acetyl-CoA to
CC produce acetoacetyl-CoA (PubMed:1685080, PubMed:26391388). Involved in
CC solvent production (PubMed:1685080, PubMed:26391388).
CC {ECO:0000269|PubMed:1685080, ECO:0000269|PubMed:26391388}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 acetyl-CoA = acetoacetyl-CoA + CoA; Xref=Rhea:RHEA:21036,
CC ChEBI:CHEBI:57286, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.1.9;
CC Evidence={ECO:0000269|PubMed:1685080, ECO:0000269|PubMed:26391388};
CC -!- ACTIVITY REGULATION: Regulated by a redox-switch modulation. Reversibly
CC inactivated by oxidative stress through the disulfide bond formation
CC between two catalytic residues, Cys-88 and Cys-378, which enables the
CC enzyme to protect its active site from oxygen radicals and be
CC reactivated upon switching back to a reducing condition.
CC {ECO:0000269|PubMed:26391388}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:26391388}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC {ECO:0000305}.
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DR EMBL; U08465; AAA82724.1; -; Genomic_DNA.
DR EMBL; AF072734; AAC26023.1; -; Genomic_DNA.
DR EMBL; AE001437; AAK80816.1; -; Genomic_DNA.
DR PIR; E97253; E97253.
DR PIR; JC4032; JC4032.
DR RefSeq; NP_349476.1; NC_003030.1.
DR RefSeq; WP_010966157.1; NC_003030.1.
DR PDB; 4WYR; X-ray; 2.30 A; A/B=1-392.
DR PDB; 4XL2; X-ray; 1.77 A; A/B=1-392.
DR PDBsum; 4WYR; -.
DR PDBsum; 4XL2; -.
DR AlphaFoldDB; P45359; -.
DR SMR; P45359; -.
DR STRING; 272562.CA_C2873; -.
DR PRIDE; P45359; -.
DR EnsemblBacteria; AAK80816; AAK80816; CA_C2873.
DR GeneID; 44999361; -.
DR KEGG; cac:CA_C2873; -.
DR PATRIC; fig|272562.8.peg.3057; -.
DR eggNOG; COG0183; Bacteria.
DR HOGENOM; CLU_031026_0_0_9; -.
DR OMA; ICPSIAI; -.
DR OrthoDB; 1058688at2; -.
DR BioCyc; MetaCyc:THLCLOS-MON; -.
DR BRENDA; 2.3.1.9; 1452.
DR SABIO-RK; P45359; -.
DR Proteomes; UP000000814; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; IEA:UniProtKB-EC.
DR CDD; cd00751; thiolase; 1.
DR Gene3D; 3.40.47.10; -; 2.
DR InterPro; IPR002155; Thiolase.
DR InterPro; IPR016039; Thiolase-like.
DR InterPro; IPR020615; Thiolase_acyl_enz_int_AS.
DR InterPro; IPR020610; Thiolase_AS.
DR InterPro; IPR020617; Thiolase_C.
DR InterPro; IPR020613; Thiolase_CS.
DR InterPro; IPR020616; Thiolase_N.
DR Pfam; PF02803; Thiolase_C; 1.
DR Pfam; PF00108; Thiolase_N; 1.
DR PIRSF; PIRSF000429; Ac-CoA_Ac_transf; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR TIGRFAMs; TIGR01930; AcCoA-C-Actrans; 1.
DR PROSITE; PS00098; THIOLASE_1; 1.
DR PROSITE; PS00737; THIOLASE_2; 1.
DR PROSITE; PS00099; THIOLASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; Reference proteome; Transferase.
FT CHAIN 1..392
FT /note="Acetyl-CoA acetyltransferase"
FT /id="PRO_0000206403"
FT ACT_SITE 88
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000305|PubMed:26391388"
FT ACT_SITE 348
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:26391388"
FT ACT_SITE 378
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:26391388"
FT BINDING 96
FT /ligand="acetate"
FT /ligand_id="ChEBI:CHEBI:30089"
FT /evidence="ECO:0000269|PubMed:26391388,
FT ECO:0007744|PDB:4XL2"
FT BINDING 279..280
FT /ligand="acetate"
FT /ligand_id="ChEBI:CHEBI:30089"
FT /evidence="ECO:0000269|PubMed:26391388,
FT ECO:0007744|PDB:4XL2"
FT BINDING 386
FT /ligand="acetate"
FT /ligand_id="ChEBI:CHEBI:30089"
FT /evidence="ECO:0000269|PubMed:26391388,
FT ECO:0007744|PDB:4XL2"
FT DISULFID 88..378
FT /note="In inhibited form"
FT /evidence="ECO:0000269|PubMed:26391388,
FT ECO:0007744|PDB:4XL2"
FT MUTAGEN 77
FT /note="V->Q: 3-fold increase in thiolase activity, prevents
FT disulfide bond formation under oxidized condition and
FT results in the loss of regulatory mechanism based on redox-
FT switch modulation; when associated with Y-153 and K-286."
FT /evidence="ECO:0000269|PubMed:26391388"
FT MUTAGEN 153
FT /note="N->Y: 3-fold increase in thiolase activity, prevents
FT disulfide bond formation under oxidized condition and
FT results in the loss of regulatory mechanism based on redox-
FT switch modulation; when associated with Q-77 and K-286."
FT /evidence="ECO:0000269|PubMed:26391388"
FT MUTAGEN 286
FT /note="A->K: 3-fold increase in thiolase activity, prevents
FT disulfide bond formation under oxidized condition and
FT results in the loss of regulatory mechanism based on redox-
FT switch modulation; when associated with Q-77 and Y-153."
FT /evidence="ECO:0000269|PubMed:26391388"
FT STRAND 4..11
FT /evidence="ECO:0007829|PDB:4XL2"
FT TURN 20..23
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 26..41
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:4XL2"
FT STRAND 50..54
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 65..72
FT /evidence="ECO:0007829|PDB:4XL2"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 90..103
FT /evidence="ECO:0007829|PDB:4XL2"
FT STRAND 108..118
FT /evidence="ECO:0007829|PDB:4XL2"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:4XL2"
FT TURN 126..130
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 142..147
FT /evidence="ECO:0007829|PDB:4XL2"
FT TURN 151..154
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 157..168
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 172..191
FT /evidence="ECO:0007829|PDB:4XL2"
FT TURN 192..198
FT /evidence="ECO:0007829|PDB:4XL2"
FT STRAND 202..205
FT /evidence="ECO:0007829|PDB:4XL2"
FT STRAND 210..213
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 225..229
FT /evidence="ECO:0007829|PDB:4XL2"
FT STRAND 233..236
FT /evidence="ECO:0007829|PDB:4XL2"
FT STRAND 242..246
FT /evidence="ECO:0007829|PDB:4WYR"
FT STRAND 250..260
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 261..266
FT /evidence="ECO:0007829|PDB:4XL2"
FT STRAND 272..279
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 285..290
FT /evidence="ECO:0007829|PDB:4WYR"
FT HELIX 294..302
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:4XL2"
FT STRAND 311..315
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 320..330
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 334..336
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 343..346
FT /evidence="ECO:0007829|PDB:4XL2"
FT HELIX 350..368
FT /evidence="ECO:0007829|PDB:4XL2"
FT STRAND 372..377
FT /evidence="ECO:0007829|PDB:4XL2"
FT TURN 381..383
FT /evidence="ECO:0007829|PDB:4XL2"
FT STRAND 385..391
FT /evidence="ECO:0007829|PDB:4XL2"
SQ SEQUENCE 392 AA; 41241 MW; 024D9B21D200856D CRC64;
MKEVVIASAV RTAIGSYGKS LKDVPAVDLG ATAIKEAVKK AGIKPEDVNE VILGNVLQAG
LGQNPARQAS FKAGLPVEIP AMTINKVCGS GLRTVSLAAQ IIKAGDADVI IAGGMENMSR
APYLANNARW GYRMGNAKFV DEMITDGLWD AFNDYHMGIT AENIAERWNI SREEQDEFAL
ASQKKAEEAI KSGQFKDEIV PVVIKGRKGE TVVDTDEHPR FGSTIEGLAK LKPAFKKDGT
VTAGNASGLN DCAAVLVIMS AEKAKELGVK PLAKIVSYGS AGVDPAIMGY GPFYATKAAI
EKAGWTVDEL DLIESNEAFA AQSLAVAKDL KFDMNKVNVN GGAIALGHPI GASGARILVT
LVHAMQKRDA KKGLATLCIG GGQGTAILLE KC
