ID ACSA_SALTY Reviewed; 652 AA. AC Q8ZKF6; DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2002, sequence version 1. DT 27-MAR-2024, entry version 124. DE RecName: Full=Acetyl-coenzyme A synthetase {ECO:0000255|HAMAP-Rule:MF_01123}; DE Short=AcCoA synthetase {ECO:0000255|HAMAP-Rule:MF_01123}; DE Short=Acs {ECO:0000255|HAMAP-Rule:MF_01123}; DE EC=6.2.1.1 {ECO:0000255|HAMAP-Rule:MF_01123}; DE AltName: Full=Acetate--CoA ligase {ECO:0000255|HAMAP-Rule:MF_01123}; DE AltName: Full=Acyl-activating enzyme {ECO:0000255|HAMAP-Rule:MF_01123}; GN Name=acs {ECO:0000255|HAMAP-Rule:MF_01123}; OrderedLocusNames=STM4275; OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Enterobacteriaceae; Salmonella. OX NCBI_TaxID=99287; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=LT2 / SGSC1412 / ATCC 700720; RX PubMed=11677609; DOI=10.1038/35101614; RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P., RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D., RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E., RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R., RA Wilson R.K.; RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2."; RL Nature 413:852-856(2001). RN [2] RP ACETYLATION AT LYS-609, AND DEACETYLATION BY SIR2 HOMOLOG. RC STRAIN=LT2 / SGSC1412 / ATCC 700720; RX PubMed=12493915; DOI=10.1126/science.1077650; RA Starai V.J., Celic I., Cole R.N., Boeke J.D., Escalante-Semerena J.C.; RT "Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of RT active lysine."; RL Science 298:2390-2392(2002). RN [3] RP ACETYLATION AT LYS-609. RC STRAIN=LT2; RX PubMed=15236963; DOI=10.1016/j.jmb.2004.05.010; RA Starai V.J., Escalante-Semerena J.C.; RT "Identification of the protein acetyltransferase (Pat) enzyme that RT acetylates acetyl-CoA synthetase in Salmonella enterica."; RL J. Mol. Biol. 340:1005-1012(2004). RN [4] RP FUNCTION. RC STRAIN=LT2; RX PubMed=16272400; DOI=10.1099/mic.0.28156-0; RA Starai V.J., Garrity J., Escalante-Semerena J.C.; RT "Acetate excretion during growth of Salmonella enterica on ethanolamine RT requires phosphotransacetylase (EutD) activity, and acetate recapture RT requires acetyl-CoA synthetase (Acs) and phosphotransacetylase (Pta) RT activities."; RL Microbiology 151:3793-3801(2005). RN [5] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH ATP ANALOG AND RP COENZYME A, AND SUBUNIT. RX PubMed=12627952; DOI=10.1021/bi0271603; RA Gulick A.M., Starai V.J., Horswill A.R., Homick K.M., RA Escalante-Semerena J.C.; RT "The 1.75 A crystal structure of acetyl-CoA synthetase bound to adenosine- RT 5'-propylphosphate and coenzyme A."; RL Biochemistry 42:2866-2873(2003). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.42 ANGSTROMS) OF WILD-TYPE AND MUTANTS IN COMPLEX RP WITH THE ATP ANALOG AMP; COENZYME A AND MAGNESIUM IONS, FUNCTION, RP MUTAGENESIS OF ARG-194; ALA-357; ASP-517; GLY-524; ARG-526; ARG-584 AND RP LYS-609, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT. RX PubMed=17497934; DOI=10.1021/bi6026506; RA Reger A.S., Carney J.M., Gulick A.M.; RT "Biochemical and crystallographic analysis of substrate binding and RT conformational changes in acetyl-CoA synthetase."; RL Biochemistry 46:6536-6546(2007). CC -!- FUNCTION: Catalyzes the conversion of acetate into acetyl-CoA (AcCoA), CC an essential intermediate at the junction of anabolic and catabolic CC pathways. Acs undergoes a two-step reaction. In the first half CC reaction, Acs combines acetate with ATP to form acetyl-adenylate CC (AcAMP) intermediate. In the second half reaction, it can then transfer CC the acetyl group from AcAMP to the sulfhydryl group of CoA, forming the CC product AcCoA. Required for acetate recapture but not for acetate CC excretion when this organism is grown on ethanolamine CC (PubMed:16272400). {ECO:0000255|HAMAP-Rule:MF_01123, CC ECO:0000269|PubMed:16272400, ECO:0000269|PubMed:17497934}. CC -!- FUNCTION: Enables the cell to use acetate during aerobic growth to CC generate energy via the TCA cycle, and biosynthetic compounds via the CC glyoxylate shunt. Acetylates CheY, the response regulator involved in CC flagellar movement and chemotaxis. {ECO:0000255|HAMAP-Rule:MF_01123}. CC -!- CATALYTIC ACTIVITY: CC Reaction=acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate; CC Xref=Rhea:RHEA:23176, ChEBI:CHEBI:30089, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, CC ChEBI:CHEBI:456215; EC=6.2.1.1; Evidence={ECO:0000255|HAMAP- CC Rule:MF_01123}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=77.1 uM for ATP (at pH 7.5 and at 37 degrees Celsius) CC {ECO:0000269|PubMed:17497934}; CC KM=50 uM for CoA (at pH 7.5 and at 37 degrees Celsius) CC {ECO:0000269|PubMed:17497934}; CC KM=6047 uM for acetate (at pH 7.5 and at 37 degrees Celsius) CC {ECO:0000269|PubMed:17497934}; CC KM=9413 uM for propionate (at pH 7.5 and at 37 degrees Celsius) CC {ECO:0000269|PubMed:17497934}; CC KM=9450 uM for glycine (at pH 7.5 and at 37 degrees Celsius) CC {ECO:0000269|PubMed:17497934}; CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:12627952, CC ECO:0000269|PubMed:17497934}. CC -!- PTM: Acetylated. Deacetylation by the SIR2-homolog deacetylase CC activates the enzyme. {ECO:0000255|HAMAP-Rule:MF_01123, CC ECO:0000269|PubMed:12493915, ECO:0000269|PubMed:15236963}. CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family. CC {ECO:0000255|HAMAP-Rule:MF_01123}. 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; AE006468; AAL23099.1; -; Genomic_DNA. DR RefSeq; NP_463140.1; NC_003197.2. DR RefSeq; WP_000083882.1; NC_003197.2. DR PDB; 1PG3; X-ray; 2.30 A; A/B=1-652. DR PDB; 1PG4; X-ray; 1.75 A; A/B=1-652. DR PDB; 2P20; X-ray; 2.22 A; A/B=1-652. DR PDB; 2P2B; X-ray; 2.20 A; A/B=1-652. DR PDB; 2P2F; X-ray; 2.58 A; A/B=1-652. DR PDB; 2P2J; X-ray; 2.30 A; A/B=1-652. DR PDB; 2P2M; X-ray; 2.11 A; A/B=1-652. DR PDB; 2P2Q; X-ray; 2.42 A; A/B=1-652. DR PDB; 5JRH; X-ray; 1.64 A; A/B=1-652. DR PDBsum; 1PG3; -. DR PDBsum; 1PG4; -. DR PDBsum; 2P20; -. DR PDBsum; 2P2B; -. DR PDBsum; 2P2F; -. DR PDBsum; 2P2J; -. DR PDBsum; 2P2M; -. DR PDBsum; 2P2Q; -. DR PDBsum; 5JRH; -. DR AlphaFoldDB; Q8ZKF6; -. DR SMR; Q8ZKF6; -. DR STRING; 99287.STM4275; -. DR DrugBank; DB03230; Adenosine-5'-Propylphosphate. DR DrugBank; DB01992; Coenzyme A. DR iPTMnet; Q8ZKF6; -. DR PaxDb; 99287-STM4275; -. DR GeneID; 1255801; -. DR KEGG; stm:STM4275; -. DR PATRIC; fig|99287.12.peg.4496; -. DR HOGENOM; CLU_000022_3_6_6; -. DR OMA; INVSYNC; -. DR PhylomeDB; Q8ZKF6; -. DR BioCyc; SENT99287:STM4275-MONOMER; -. DR SABIO-RK; Q8ZKF6; -. DR EvolutionaryTrace; Q8ZKF6; -. DR Proteomes; UP000001014; Chromosome. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0003987; F:acetate-CoA ligase activity; IDA:CACAO. DR GO; GO:0016208; F:AMP binding; IEA:InterPro. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006085; P:acetyl-CoA biosynthetic process; IBA:GO_Central. DR GO; GO:0019427; P:acetyl-CoA biosynthetic process from acetate; IEA:UniProtKB-UniRule. DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-UniRule. DR CDD; cd05966; ACS; 1. DR Gene3D; 3.30.300.30; -; 1. DR Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 1. DR HAMAP; MF_01123; Ac_CoA_synth; 1. DR InterPro; IPR011904; Ac_CoA_lig. DR InterPro; IPR032387; ACAS_N. DR InterPro; IPR025110; AMP-bd_C. DR InterPro; IPR045851; AMP-bd_C_sf. DR InterPro; IPR020845; AMP-binding_CS. DR InterPro; IPR000873; AMP-dep_Synth/Lig_com. DR InterPro; IPR042099; ANL_N_sf. DR NCBIfam; TIGR02188; Ac_CoA_lig_AcsA; 1. DR PANTHER; PTHR24095; ACETYL-COENZYME A SYNTHETASE; 1. DR PANTHER; PTHR24095:SF243; ACETYL-COENZYME A SYNTHETASE; 1. DR Pfam; PF16177; ACAS_N; 1. DR Pfam; PF00501; AMP-binding; 1. DR Pfam; PF13193; AMP-binding_C; 1. DR SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1. DR PROSITE; PS00455; AMP_BINDING; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Ligase; Magnesium; Metal-binding; KW Nucleotide-binding; Reference proteome. FT CHAIN 1..652 FT /note="Acetyl-coenzyme A synthetase" FT /id="PRO_0000208386" FT BINDING 191..194 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT BINDING 311 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123, FT ECO:0000269|PubMed:12627952, ECO:0000269|PubMed:17497934" FT BINDING 335 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123, FT ECO:0000269|PubMed:12627952, ECO:0000269|PubMed:17497934" FT BINDING 387..389 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 411..416 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 500 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 515 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 523 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123, FT ECO:0000269|PubMed:12627952, ECO:0000269|PubMed:17497934" FT BINDING 526 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 537 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT BINDING 539 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT BINDING 542 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT BINDING 584 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123, FT ECO:0000269|PubMed:12627952, ECO:0000269|PubMed:17497934" FT SITE 517 FT /note="Hinge residue important for conformational FT flexibility" FT MOD_RES 609 FT /note="N6-acetyllysine; by Pat" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123, FT ECO:0000269|PubMed:12493915, ECO:0000269|PubMed:15236963" FT MUTAGEN 194 FT /note="R->A: Results in a 2-fold reduction in the catalytic FT efficiency for both ATP and CoA. 2-fold increase in the FT affinity for ATP and 3-fold reduction for CoA." FT /evidence="ECO:0000269|PubMed:17497934" FT MUTAGEN 194 FT /note="R->E: Results in a 2-fold reduction in the catalytic FT efficiency for both ATP and CoA. 2-fold increase in the FT affinity for ATP and 2-fold reduction for CoA." FT /evidence="ECO:0000269|PubMed:17497934" FT MUTAGEN 357 FT /note="A->V: Results in a 2-fold reduction in the catalytic FT efficiency for both ATP and CoA. 3-fold increase in the FT affinity for ATP and 3-fold reduction for CoA." FT /evidence="ECO:0000269|PubMed:17497934" FT MUTAGEN 517 FT /note="D->G: Results in a 2-fold reduction in the catalytic FT efficiency for both ATP and CoA. 2-fold increase in the FT affinity for ATP and 10-fold reduction for CoA." FT /evidence="ECO:0000269|PubMed:17497934" FT MUTAGEN 517 FT /note="D->P: Results in a 2-fold reduction in the catalytic FT efficiency for both ATP and CoA. 3-fold reduction in the FT affinity for ATP and 4.5-fold reduction for CoA." FT /evidence="ECO:0000269|PubMed:17497934" FT MUTAGEN 524 FT /note="G->L: No acetyl-coenzyme A synthetase activity." FT /evidence="ECO:0000269|PubMed:17497934" FT MUTAGEN 524 FT /note="G->S: Results in a 2-fold reduction in the catalytic FT efficiency for both ATP and CoA. Almost the same affinity FT as the wild-type for ATP, but 9-fold reduction in the FT affinity for CoA." FT /evidence="ECO:0000269|PubMed:17497934" FT MUTAGEN 526 FT /note="R->A: Results in a 2-fold reduction in the catalytic FT efficiency for both ATP and CoA. 3-fold increase in the FT affinity for ATP and 4-fold reduction for CoA." FT /evidence="ECO:0000269|PubMed:17497934" FT MUTAGEN 584 FT /note="R->A: Results in a 2-fold reduction in the catalytic FT efficiency for both ATP and CoA. 2-fold increase in the FT affinity for ATP and 7-fold reduction for CoA." FT /evidence="ECO:0000269|PubMed:17497934" FT MUTAGEN 584 FT /note="R->E: Results in a 2-fold reduction in the catalytic FT efficiency for both ATP and CoA. 3-fold increase in the FT affinity for ATP and 8-fold reduction for CoA." FT /evidence="ECO:0000269|PubMed:17497934" FT MUTAGEN 609 FT /note="K->A: No acetyl-coenzyme A synthetase activity." FT /evidence="ECO:0000269|PubMed:17497934" FT HELIX 11..16 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 21..33 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 35..42 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 43..45 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 56..59 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 66..70 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 77..81 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 83..85 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 86..89 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 92..98 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 105..109 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 110..126 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 134..138 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 143..155 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 158..161 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 168..178 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 181..187 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 189..191 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 194..196 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 198..206 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 216..220 FT /evidence="ECO:0007829|PDB:5JRH" FT TURN 231..233 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 234..236 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 237..243 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 257..264 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 267..270 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 272..278 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 279..292 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 300..303 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 310..314 FT /evidence="ECO:0007829|PDB:5JRH" FT TURN 315..317 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 318..322 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 326..330 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 336..338 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 341..349 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 352..356 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 358..365 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 366..371 FT /evidence="ECO:0007829|PDB:5JRH" FT TURN 372..374 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 382..388 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 392..401 FT /evidence="ECO:0007829|PDB:5JRH" FT TURN 402..405 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 409..413 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 416..418 FT /evidence="ECO:0007829|PDB:5JRH" FT TURN 427..429 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 438..440 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 446..449 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 458..466 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 481..489 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 490..492 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 495..504 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 510..522 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 525..528 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 529..537 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 542..552 FT /evidence="ECO:0007829|PDB:5JRH" FT TURN 553..555 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 556..565 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 573..586 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 589..591 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 594..598 FT /evidence="ECO:0007829|PDB:5JRH" FT STRAND 604..607 FT /evidence="ECO:0007829|PDB:2P2M" FT HELIX 612..620 FT /evidence="ECO:0007829|PDB:5JRH" FT HELIX 629..631 FT /evidence="ECO:0007829|PDB:1PG4" FT STRAND 632..634 FT /evidence="ECO:0007829|PDB:2P2M" FT HELIX 637..646 FT /evidence="ECO:0007829|PDB:5JRH" SQ SEQUENCE 652 AA; 72153 MW; 347209D1D3D349D8 CRC64; MSQTHKHAIP ANIADRCLIN PEQYETKYKQ SINDPDTFWG EQGKILDWIT PYQKVKNTSF APGNVSIKWY EDGTLNLAAN CLDRHLQENG DRTAIIWEGD DTSQSKHISY RELHRDVCRF ANTLLDLGIK KGDVVAIYMP MVPEAAVAML ACARIGAVHS VIFGGFSPEA VAGRIIDSSS RLVITADEGV RAGRSIPLKK NVDDALKNPN VTSVEHVIVL KRTGSDIDWQ EGRDLWWRDL IEKASPEHQP EAMNAEDPLF ILYTSGSTGK PKGVLHTTGG YLVYAATTFK YVFDYHPGDI YWCTADVGWV TGHSYLLYGP LACGATTLMF EGVPNWPTPA RMCQVVDKHQ VNILYTAPTA IRALMAEGDK AIEGTDRSSL RILGSVGEPI NPEAWEWYWK KIGKEKCPVV DTWWQTETGG FMITPLPGAI ELKAGSATRP FFGVQPALVD NEGHPQEGAT EGNLVITDSW PGQARTLFGD HERFEQTYFS TFKNMYFSGD GARRDEDGYY WITGRVDDVL NVSGHRLGTA EIESALVAHP KIAEAAVVGI PHAIKGQAIY AYVTLNHGEE PSPELYAEVR NWVRKEIGPL ATPDVLHWTD SLPKTRSGKI MRRILRKIAA GDTSNLGDTS TLADPGVVEK LLEEKQAIAM PS //