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 27-MAR-2024, entry version 143. 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; Bacillota; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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 OrthoDB; 9764892at2; -. DR BioCyc; MetaCyc:THLCLOS-MONOMER; -. 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 NCBIfam; TIGR01930; AcCoA-C-Actrans; 1. DR PANTHER; PTHR18919; ACETYL-COA C-ACYLTRANSFERASE; 1. DR PANTHER; PTHR18919:SF153; TRIFUNCTIONAL ENZYME SUBUNIT BETA, MITOCHONDRIAL; 1. DR Pfam; PF02803; Thiolase_C; 1. DR Pfam; PF00108; Thiolase_N; 1. DR PIRSF; PIRSF000429; Ac-CoA_Ac_transf; 1. DR SUPFAM; SSF53901; Thiolase-like; 2. 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 //