ACSA_MYCTU
ID ACSA_MYCTU Reviewed; 651 AA.
AC P9WQD1; L0TGD8; O69635;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
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=acsA {ECO:0000255|HAMAP-Rule:MF_01123}; Synonyms=acs;
GN OrderedLocusNames=Rv3667; ORFNames=MTV025.015;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION, AUTOACETYLATION AT LYS-617, MUTAGENESIS OF LYS-617,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RX PubMed=21896569; DOI=10.1093/abbs/gmr076;
RA Li R., Gu J., Chen P., Zhang Z., Deng J., Zhang X.;
RT "Purification and characterization of the acetyl-CoA synthetase from
RT Mycobacterium tuberculosis.";
RL Acta Biochim. Biophys. Sin. 43:891-899(2011).
RN [3]
RP FUNCTION, ACETYLATION AT LYS-617, AND MUTAGENESIS OF LYS-617.
RX PubMed=21627103; DOI=10.1021/bi200156t;
RA Xu H., Hegde S.S., Blanchard J.S.;
RT "Reversible acetylation and inactivation of Mycobacterium tuberculosis
RT acetyl-CoA synthetase is dependent on cAMP.";
RL Biochemistry 50:5883-5892(2011).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: Catalyzes the conversion of acetate into acetyl-CoA (AcCoA),
CC an essential intermediate at the junction of anabolic and catabolic
CC pathways. AcsA undergoes a two-step reaction. In the first half
CC reaction, AcsA 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. M.tuberculosis may use AcsA for both acetate and
CC propionate assimilation. {ECO:0000255|HAMAP-Rule:MF_01123,
CC ECO:0000269|PubMed:21627103, ECO:0000269|PubMed:21896569}.
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 Evidence={ECO:0000255|HAMAP-Rule:MF_01123,
CC ECO:0000269|PubMed:21896569};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01123,
CC ECO:0000269|PubMed:21896569};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01123,
CC ECO:0000269|PubMed:21896569};
CC Name=Ni(2+); Xref=ChEBI:CHEBI:49786;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01123,
CC ECO:0000269|PubMed:21896569};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01123,
CC ECO:0000269|PubMed:21896569};
CC Note=Magnesium, but can also use calcium, manganese, nickel or zinc
CC ions. {ECO:0000255|HAMAP-Rule:MF_01123, ECO:0000269|PubMed:21896569};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.35 mM for CoA (at pH 8 and at 37 degrees Celsius)
CC {ECO:0000269|PubMed:21896569};
CC KM=1.2 mM for acetate (at pH 8 and at 37 degrees Celsius)
CC {ECO:0000269|PubMed:21896569};
CC KM=2.1 mM for propionate (at pH 8 and at 37 degrees Celsius)
CC {ECO:0000269|PubMed:21896569};
CC KM=5.6 mM for ATP (at pH 8 and at 37 degrees Celsius)
CC {ECO:0000269|PubMed:21896569};
CC KM=509 mM for butyrate (at pH 8 and at 37 degrees Celsius)
CC {ECO:0000269|PubMed:21896569};
CC pH dependence:
CC Optimum pH is around 8. The enzyme is stable under neutral and
CC alkaline conditions, while its activity decreases rapidly below pH
CC 6.0. {ECO:0000269|PubMed:21896569};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius. It lost its activity
CC rapidly below 25 degrees Celsius or above 45 degrees Celsius.
CC {ECO:0000269|PubMed:21896569};
CC -!- PTM: Acetylated on Lys-617 by Pat in the presence of acetyl-CoA as an
CC acetyl donor and ATP. Acetylation results in the inactivation of the
CC enzyme. Deacetylation by the SIR2-homolog deacetylase CobB is required
CC to activate the enzyme. {ECO:0000269|PubMed:21627103}.
CC -!- MISCELLANEOUS: Could be also autoacetylated on Lys-617 in the presence
CC of acetate as an acetyl donor and ATP. Autoacetylation is effectively
CC inhibited by CoA. If CoA is not available or the concentration of CoA
CC is low in vivo, the enzyme can transfer acetyl group from AcAMP to
CC itself, resulting in autoacetylation and inactivation. When CoA is
CC available, the acetyl group is donated to CoA forming AcCoA
CC (PubMed:21896569). {ECO:0000305|PubMed:21896569}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000255|HAMAP-Rule:MF_01123}.
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DR EMBL; AL123456; CCP46490.1; -; Genomic_DNA.
DR PIR; D70789; D70789.
DR RefSeq; NP_218184.1; NC_000962.3.
DR RefSeq; WP_003899631.1; NZ_NVQJ01000028.1.
DR AlphaFoldDB; P9WQD1; -.
DR SMR; P9WQD1; -.
DR STRING; 83332.Rv3667; -.
DR iPTMnet; P9WQD1; -.
DR PaxDb; P9WQD1; -.
DR DNASU; 885479; -.
DR GeneID; 885479; -.
DR KEGG; mtu:Rv3667; -.
DR TubercuList; Rv3667; -.
DR eggNOG; COG0365; Bacteria.
DR OMA; DHWWHDL; -.
DR PhylomeDB; P9WQD1; -.
DR SABIO-RK; P9WQD1; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0003987; F:acetate-CoA ligase activity; IBA:GO_Central.
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:InterPro.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 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.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF16177; ACAS_N; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR TIGRFAMs; TIGR02188; Ac_CoA_lig_AcsA; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Ligase; Magnesium; Metal-binding;
KW Nucleotide-binding; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..651
FT /note="Acetyl-coenzyme A synthetase"
FT /id="PRO_0000208369"
FT BINDING 190..193
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123"
FT BINDING 311
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123"
FT BINDING 387..389
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123"
FT BINDING 411..416
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123"
FT BINDING 508
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123"
FT BINDING 523
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123"
FT BINDING 531
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123"
FT BINDING 534
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123"
FT BINDING 545
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123"
FT BINDING 547
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123"
FT BINDING 550
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT MOD_RES 617
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01123,
FT ECO:0000269|PubMed:21627103"
FT MUTAGEN 617
FT /note="K->R: Complete loss of acetyl-coenzyme A synthetase
FT activity."
FT /evidence="ECO:0000269|PubMed:21627103,
FT ECO:0000269|PubMed:21896569"
SQ SEQUENCE 651 AA; 71476 MW; 94290C0517A0445B CRC64;
MSESTPEVSS SYPPPAHFAE HANARAELYR EAEEDRLAFW AKQANRLSWT TPFTEVLDWS
GAPFAKWFVG GELNVAYNCV DRHVEAGHGD RVAIHWEGEP VGDRRTLTYS DLLAEVSKAA
NALTDLGLVA GDRVAIYLPL IPEAVIAMLA CARLGIMHSV VFGGFTAAAL QARIVDAQAK
LLITADGQFR RGKPSPLKAA ADEALAAIPD CSVEHVLVVR RTGIEMAWSE GRDLWWHHVV
GSASPAHTPE PFDSEHPLFL LYTSGTTGKP KGIMHTSGGY LTQCCYTMRT IFDVKPDSDV
FWCTADIGWV TGHTYGVYGP LCNGVTEVLY EGTPDTPDRH RHFQIIEKYG VTIYYTAPTL
IRMFMKWGRE IPDSHDLSSL RLLGSVGEPI NPEAWRWYRD VIGGGRTPLV DTWWQTETGS
AMISPLPGIA AAKPGSAMTP LPGISAKIVD DHGDPLPPHT EGAQHVTGYL VLDQPWPSML
RGIWGDPARY WHSYWSKFSD KGYYFAGDGA RIDPDGAIWV LGRIDDVMNV SGHRISTAEV
ESALVAHSGV AEAAVVGVTD ETTTQAICAF VVLRANYAPH DRTAEELRTE VARVISPIAR
PRDVHVVPEL PKTRSGKIMR RLLRDVAENR ELGDTSTLLD PTVFDAIRAA K
