THIL_SHIZO
ID THIL_SHIZO Reviewed; 392 AA.
AC P07097;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Acetyl-CoA acetyltransferase;
DE EC=2.3.1.9;
DE AltName: Full=Acetoacetyl-CoA thiolase;
DE AltName: Full=Beta-ketothiolase {ECO:0000303|PubMed:1476773};
GN Name=phaA {ECO:0000303|PubMed:1476773};
GN Synonyms=phbA {ECO:0000303|PubMed:2670935};
OS Shinella zoogloeoides (Crabtreella saccharophila).
OC Bacteria; Proteobacteria; Alphaproteobacteria; Hyphomicrobiales;
OC Rhizobiaceae; Shinella.
OX NCBI_TaxID=352475;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 19623 / DSM 287 / JCM 20728 / IAM 12669 / NBRC 102405 / NCIMB
RC 10340 / NCTC 10482 / NRRL B-3303 / I-16-M;
RX PubMed=2878929; DOI=10.1016/s0021-9258(19)75893-1;
RA Peoples O.P., Masamune S., Walsh C.T., Sinskey A.J.;
RT "Biosynthetic thiolase from Zoogloea ramigera. III. Isolation and
RT characterization of the structural gene.";
RL J. Biol. Chem. 262:97-102(1987).
RN [2]
RP SEQUENCE REVISION TO 131.
RX PubMed=2670935; DOI=10.1016/s0021-9258(19)84824-x;
RA Peoples O.P., Sinskey A.J.;
RT "Poly-beta-hydroxybutyrate biosynthesis in Alcaligenes eutrophus H16.
RT Characterization of the genes encoding beta-ketothiolase and acetoacetyl-
RT CoA reductase.";
RL J. Biol. Chem. 264:15293-15297(1989).
RN [3]
RP MUTAGENESIS OF CYS-378.
RX PubMed=1673680; DOI=10.1016/s0021-9258(18)92985-6;
RA Palmer M.A.J., Differding E., Gamboni R., Williams S.F., Peoples O.P.,
RA Walsh C.T., Sinskey S.J., Masamune S.;
RT "Biosynthetic thiolase from Zoogloea ramigera. Evidence for a mechanism
RT involving Cys-378 as the active site base.";
RL J. Biol. Chem. 266:8369-8375(1991).
RN [4]
RP GENE NAME.
RX PubMed=1476773; DOI=10.1111/j.1574-6968.1992.tb05841.x;
RA Steinbuechel A., Hustede E., Liebergesell M., Pieper U., Timm A.,
RA Valentin H.;
RT "Molecular basis for biosynthesis and accumulation of polyhydroxyalkanoic
RT acids in bacteria.";
RL FEMS Microbiol. Rev. 9:217-230(1992).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS).
RX PubMed=10764581; DOI=10.1006/jmbi.2000.3638;
RA Modis Y., Wierenga R.K.;
RT "Crystallographic analysis of the reaction pathway of Zoogloea ramigera
RT biosynthetic thiolase.";
RL J. Mol. Biol. 297:1171-1182(2000).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF THE THIOESTER INTERMEDIATE AND OF
RP COMPLEX WITH SUBSTRATE.
RX PubMed=10545327; DOI=10.1016/s0969-2126(00)80061-1;
RA Modis Y., Wierenga R.K.;
RT "A biosynthetic thiolase in complex with a reaction intermediate: the
RT crystal structure provides new insights into the catalytic mechanism.";
RL Structure 7:1279-1290(1999).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF THE THIOESTER INTERMEDIATE; OF
RP COMPLEX WITH SUBSTRATE AND OF MUTANTS ALA-64 AND ALA-89, AND MUTAGENESIS OF
RP GLN-64 AND CYS-89.
RX PubMed=12501183; DOI=10.1021/bi0266232;
RA Kursula P., Ojala J., Lambeir A.-M., Wierenga R.K.;
RT "The catalytic cycle of biosynthetic thiolase: a conformational journey of
RT an acetyl group through four binding modes and two oxyanion holes.";
RL Biochemistry 41:15543-15556(2002).
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:0000255|PROSITE-ProRule:PRU10020};
CC -!- PATHWAY: Biopolymer metabolism; poly-(R)-3-hydroxybutanoate
CC biosynthesis. {ECO:0000305}.
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 1/3.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:10545327,
CC ECO:0000269|PubMed:10764581, ECO:0000269|PubMed:12501183}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC {ECO:0000305}.
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DR EMBL; J02631; AAA27706.1; ALT_SEQ; Genomic_DNA.
DR PIR; A26121; XXGZAC.
DR PDB; 1DLU; X-ray; 2.25 A; A/B/C/D=5-392.
DR PDB; 1DLV; X-ray; 2.29 A; A/B/C/D=5-392.
DR PDB; 1DM3; X-ray; 2.00 A; A/B/C/D=5-392.
DR PDB; 1M1O; X-ray; 1.95 A; A/B/C/D=2-392.
DR PDB; 1M1T; X-ray; 1.94 A; A/B/C/D=2-392.
DR PDB; 1M3K; X-ray; 1.70 A; A/B/C/D=2-392.
DR PDB; 1M3Z; X-ray; 1.87 A; A/B/C/D=2-392.
DR PDB; 1M4S; X-ray; 1.87 A; A/B/C/D=2-392.
DR PDB; 1M4T; X-ray; 1.77 A; A/B/C/D=2-392.
DR PDB; 1NL7; X-ray; 1.90 A; A/B/C/D=2-392.
DR PDB; 1OU6; X-ray; 2.07 A; A/B/C/D=2-392.
DR PDB; 1QFL; X-ray; 1.92 A; A/B/C/D=5-392.
DR PDB; 2VTZ; X-ray; 2.30 A; A/B/C/D=2-392.
DR PDB; 2VU0; X-ray; 1.87 A; A/B/C/D=2-392.
DR PDB; 2VU1; X-ray; 1.51 A; A/B/C/D=12-392.
DR PDB; 2VU2; X-ray; 2.65 A; A/B/C/D=2-392.
DR PDB; 2WKT; X-ray; 2.00 A; A/B/C/D=2-392.
DR PDB; 2WKU; X-ray; 2.30 A; A/B/C/D=2-392.
DR PDB; 2WKV; X-ray; 2.50 A; A/B/C/D=2-392.
DR PDB; 2WL4; X-ray; 1.80 A; A/B/C/D=2-392.
DR PDB; 2WL5; X-ray; 1.80 A; A/B/C/D=2-392.
DR PDB; 2WL6; X-ray; 2.98 A; A/B/C/D=2-392.
DR PDB; 7LBZ; X-ray; 2.60 A; A/B/C/D=2-392.
DR PDB; 7LCA; X-ray; 2.00 A; A/B/C/D=2-392.
DR PDB; 7LCL; X-ray; 2.29 A; A/B/C/D=2-392.
DR PDB; 7LD2; X-ray; 2.80 A; A/B/C/D=2-392.
DR PDB; 7LDC; X-ray; 2.50 A; A/B/C/D=2-392.
DR PDB; 7LDT; X-ray; 2.60 A; A/B/C/D=2-392.
DR PDB; 7LDU; X-ray; 2.85 A; A/B/C/D=2-392.
DR PDB; 7LDV; X-ray; 2.90 A; A/B/C/D=2-392.
DR PDB; 7LDW; X-ray; 2.50 A; A/B/C/D=2-392.
DR PDBsum; 1DLU; -.
DR PDBsum; 1DLV; -.
DR PDBsum; 1DM3; -.
DR PDBsum; 1M1O; -.
DR PDBsum; 1M1T; -.
DR PDBsum; 1M3K; -.
DR PDBsum; 1M3Z; -.
DR PDBsum; 1M4S; -.
DR PDBsum; 1M4T; -.
DR PDBsum; 1NL7; -.
DR PDBsum; 1OU6; -.
DR PDBsum; 1QFL; -.
DR PDBsum; 2VTZ; -.
DR PDBsum; 2VU0; -.
DR PDBsum; 2VU1; -.
DR PDBsum; 2VU2; -.
DR PDBsum; 2WKT; -.
DR PDBsum; 2WKU; -.
DR PDBsum; 2WKV; -.
DR PDBsum; 2WL4; -.
DR PDBsum; 2WL5; -.
DR PDBsum; 2WL6; -.
DR PDBsum; 7LBZ; -.
DR PDBsum; 7LCA; -.
DR PDBsum; 7LCL; -.
DR PDBsum; 7LD2; -.
DR PDBsum; 7LDC; -.
DR PDBsum; 7LDT; -.
DR PDBsum; 7LDU; -.
DR PDBsum; 7LDV; -.
DR PDBsum; 7LDW; -.
DR AlphaFoldDB; P07097; -.
DR SMR; P07097; -.
DR DrugBank; DB08408; (3R)-3-hydroxy-2,2-dimethyl-4-oxo-4-({3-oxo-3-[(2-sulfanylethyl)amino]propyl}amino)butyl 2,2-dimethylpropanoate.
DR DrugBank; DB03059; Acetoacetyl-CoA.
DR DrugBank; DB01992; Coenzyme A.
DR DrugBank; DB08328; PANTOTHENYL-AMINOETHANOL-11-PIVALIC ACID.
DR DrugBank; DB03045; Pantothenyl-Aminoethanol-Acetate Pivalic Acid.
DR DrugBank; DB02039; S-Acetyl-Cysteine.
DR DrugBank; DB02160; S-Butyryl-Cystein.
DR DrugBank; DB01915; S-Hydroxycysteine.
DR BRENDA; 2.3.1.9; 6758.
DR SABIO-RK; P07097; -.
DR UniPathway; UPA00058; UER00101.
DR UniPathway; UPA00917; -.
DR EvolutionaryTrace; P07097; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0042619; P:poly-hydroxybutyrate biosynthetic process; IEA:UniProtKB-KW.
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; PHB biosynthesis; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..392
FT /note="Acetyl-CoA acetyltransferase"
FT /id="PRO_0000206463"
FT ACT_SITE 89
FT /note="Acyl-thioester intermediate"
FT ACT_SITE 348
FT /note="Proton acceptor"
FT ACT_SITE 378
FT /note="Proton acceptor"
FT MUTAGEN 64
FT /note="Q->A: Slightly lower activity."
FT /evidence="ECO:0000269|PubMed:12501183"
FT MUTAGEN 89
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12501183"
FT MUTAGEN 378
FT /note="C->G: Loss of activity."
FT /evidence="ECO:0000269|PubMed:1673680"
FT STRAND 6..12
FT /evidence="ECO:0007829|PDB:2VU1"
FT TURN 21..24
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 27..42
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 66..73
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 80..86
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 91..104
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 111..119
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:1M3K"
FT STRAND 137..141
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 142..147
FT /evidence="ECO:0007829|PDB:2VU1"
FT TURN 151..153
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 157..168
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 172..192
FT /evidence="ECO:0007829|PDB:2VU1"
FT TURN 193..198
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 202..204
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:7LCA"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 225..229
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:2WL4"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 250..260
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 261..267
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 272..282
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 285..290
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 292..303
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 311..315
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 320..330
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 334..336
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 343..346
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:2VU1"
FT HELIX 353..368
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 371..379
FT /evidence="ECO:0007829|PDB:2VU1"
FT TURN 380..382
FT /evidence="ECO:0007829|PDB:2VU1"
FT STRAND 383..390
FT /evidence="ECO:0007829|PDB:2VU1"
SQ SEQUENCE 392 AA; 40473 MW; 88A6298751A42B7E CRC64;
MSTPSIVIAS ARTAVGSFNG AFANTPAHEL GATVISAVLE RAGVAAGEVN EVILGQVLPA
GEGQNPARQA AMKAGVPQEA TAWGMNQLCG SGLRAVALGM QQIATGDASI IVAGGMESMS
MAPHCAHLAG GVKMGDFKMI DTMIKDGLTD AFYGYHMGTT AENVAKQWQL SRDEQDAFAV
ASQNKAEAAQ KDGRFKDEIV PFIVKGRKGD ITVDADEYIR HGATLDSMAK LRPAFDKEGT
VTAGNASGLN DGAAAALLMS EAEASRRGIQ PLGRIVSWAT VGVDPKVMGT GPIPASRKAL
ERAGWKIGDL DLVEANEAFA AQACAVNKDL GWDPSIVNVN GGAIAIGHPI GASGARILNT
LLFEMKRRGA RKGLATLCIG GGMGVAMCIE SL
