PAT_MYCTU
ID PAT_MYCTU Reviewed; 333 AA.
AC O05581; F2GHE2; L0T851;
DT 28-NOV-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Acetyltransferase Pat;
DE EC=2.3.1.-;
DE AltName: Full=GCN5-like enzyme;
DE AltName: Full=GCN5-related N-acetyltransferase;
DE Short=GNAT;
DE AltName: Full=Protein acetyltransferase;
DE Short=Pat;
GN OrderedLocusNames=Rv0998;
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.
RX PubMed=20507997; DOI=10.1074/jbc.m110.118398;
RA Nambi S., Basu N., Visweswariah S.S.;
RT "cAMP-regulated protein lysine acetylases in mycobacteria.";
RL J. Biol. Chem. 285:24313-24323(2010).
RN [3]
RP FUNCTION, AND ACTIVITY REGULATION.
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 IDENTIFICATION BY MASS SPECTROMETRY [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).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS,
RP CAMP AND MAGNESIUM IONS, FUNCTION, MUTAGENESIS OF HIS-173; ARG-184;
RP PHE-185; ARG-223; VAL-225 AND ALA-237, ACTIVITY REGULATION, COFACTOR, AND
RP SUBUNIT.
RX PubMed=22773105; DOI=10.1038/nsmb.2318;
RA Lee H.J., Lang P.T., Fortune S.M., Sassetti C.M., Alber T.;
RT "Cyclic AMP regulation of protein lysine acetylation in Mycobacterium
RT tuberculosis.";
RL Nat. Struct. Mol. Biol. 19:811-818(2012).
CC -!- FUNCTION: Catalyzes specifically the acetylation of the epsilon-amino
CC group of a highly conserved lysine residue in acetyl-CoA synthetase
CC (ACS). This acetylation results in the inactivation of ACS activity and
CC could be important for mycobacteria to adjust to environmental changes.
CC {ECO:0000269|PubMed:20507997, ECO:0000269|PubMed:21627103,
CC ECO:0000269|PubMed:22773105}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:22773105};
CC -!- ACTIVITY REGULATION: Autoinhibited and allosterically activated by 3,5-
CC cyclic adenosine monophosphate (cAMP). An extensive conformational
CC rearrangement relieves this autoinhibition by means of a substrate-
CC mimicking lid that covers the protein-substrate binding surface.
CC {ECO:0000269|PubMed:21627103, ECO:0000269|PubMed:22773105}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:22773105}.
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DR EMBL; AL123456; CCP43748.1; -; Genomic_DNA.
DR PIR; A70602; A70602.
DR RefSeq; NP_215513.1; NC_000962.3.
DR RefSeq; WP_003405164.1; NZ_NVQJ01000018.1.
DR PDB; 4AVA; X-ray; 1.70 A; A=1-333.
DR PDB; 4AVB; X-ray; 1.80 A; A/B=1-333.
DR PDB; 4AVC; X-ray; 2.81 A; A/B=1-333.
DR PDBsum; 4AVA; -.
DR PDBsum; 4AVB; -.
DR PDBsum; 4AVC; -.
DR AlphaFoldDB; O05581; -.
DR SMR; O05581; -.
DR STRING; 83332.Rv0998; -.
DR PaxDb; O05581; -.
DR PRIDE; O05581; -.
DR DNASU; 885385; -.
DR GeneID; 885385; -.
DR KEGG; mtu:Rv0998; -.
DR PATRIC; fig|83332.111.peg.1109; -.
DR TubercuList; Rv0998; -.
DR eggNOG; COG0664; Bacteria.
DR eggNOG; COG1670; Bacteria.
DR OMA; MVHIPGI; -.
DR PhylomeDB; O05581; -.
DR BRENDA; 2.3.1.48; 3445.
DR BRENDA; 2.3.1.B34; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016407; F:acetyltransferase activity; IDA:MTBBASE.
DR GO; GO:0016746; F:acyltransferase activity; IDA:CACAO.
DR GO; GO:0030552; F:cAMP binding; IDA:MTBBASE.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008080; F:N-acetyltransferase activity; IEA:InterPro.
DR CDD; cd00038; CAP_ED; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR018488; cNMP-bd_CS.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR Pfam; PF13302; Acetyltransf_3; 1.
DR Pfam; PF00027; cNMP_binding; 1.
DR SMART; SM00100; cNMP; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS00889; CNMP_BINDING_2; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Magnesium; Metal-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..333
FT /note="Acetyltransferase Pat"
FT /id="PRO_0000420362"
FT DOMAIN 156..318
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT BINDING 88..91
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:22773105,
FT ECO:0007744|PDB:4AVB, ECO:0007744|PDB:4AVC"
FT BINDING 98..99
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:22773105,
FT ECO:0007744|PDB:4AVB, ECO:0007744|PDB:4AVC"
FT BINDING 138
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:22773105,
FT ECO:0007744|PDB:4AVB, ECO:0007744|PDB:4AVC"
FT BINDING 173
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:22773105"
FT BINDING 214
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:22773105"
FT BINDING 238..240
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:22773105"
FT BINDING 246..251
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:22773105"
FT BINDING 277
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:22773105"
FT BINDING 286
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:22773105"
FT MUTAGEN 173
FT /note="H->K: Induces autoacetylation of the new lysine in
FT the absence of cAMP."
FT /evidence="ECO:0000269|PubMed:22773105"
FT MUTAGEN 184
FT /note="R->A: Completely abolishes the interaction with the
FT aliphatic tail of the substrate lysine."
FT /evidence="ECO:0000269|PubMed:22773105"
FT MUTAGEN 185
FT /note="F->A: Completely abolishes the interaction with the
FT aliphatic tail of the substrate lysine."
FT /evidence="ECO:0000269|PubMed:22773105"
FT MUTAGEN 223
FT /note="R->A: Substantially decreases the interaction with
FT the aliphatic tail of the substrate lysine. Markedly
FT reduced activity, with an altered pH-rate profile and
FT abolishes direct interactions with R-184."
FT /evidence="ECO:0000269|PubMed:22773105"
FT MUTAGEN 225
FT /note="V->A: Substantially decreases the interaction with
FT the aliphatic tail of the substrate lysine."
FT /evidence="ECO:0000269|PubMed:22773105"
FT MUTAGEN 237
FT /note="A->V: Completely abolishes the interaction with the
FT aliphatic tail of the substrate lysine."
FT /evidence="ECO:0000269|PubMed:22773105"
FT HELIX 12..15
FT /evidence="ECO:0007829|PDB:4AVA"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:4AVA"
FT HELIX 26..35
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 37..41
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:4AVA"
FT HELIX 89..94
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 99..106
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 108..113
FT /evidence="ECO:0007829|PDB:4AVA"
FT HELIX 115..123
FT /evidence="ECO:0007829|PDB:4AVA"
FT HELIX 127..142
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 155..160
FT /evidence="ECO:0007829|PDB:4AVA"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:4AVC"
FT HELIX 178..182
FT /evidence="ECO:0007829|PDB:4AVA"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:4AVA"
FT HELIX 193..202
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 205..214
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 217..226
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 233..240
FT /evidence="ECO:0007829|PDB:4AVA"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:4AVA"
FT HELIX 249..263
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 268..274
FT /evidence="ECO:0007829|PDB:4AVA"
FT HELIX 278..285
FT /evidence="ECO:0007829|PDB:4AVA"
FT TURN 286..288
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 292..295
FT /evidence="ECO:0007829|PDB:4AVC"
FT STRAND 298..304
FT /evidence="ECO:0007829|PDB:4AVA"
FT TURN 308..310
FT /evidence="ECO:0007829|PDB:4AVA"
FT STRAND 311..313
FT /evidence="ECO:0007829|PDB:4AVA"
FT HELIX 315..330
FT /evidence="ECO:0007829|PDB:4AVA"
SQ SEQUENCE 333 AA; 35626 MW; F66AFCDF3247331D CRC64;
MDGIAELTGA RVEDLAGMDV FQGCPAEGLV SLAASVQPLR AAAGQVLLRQ GEPAVSFLLI
SSGSAEVSHV GDDGVAIIAR ALPGMIVGEI ALLRDSPRSA TVTTIEPLTG WTGGRGAFAT
MVHIPGVGER LLRTARQRLA AFVSPIPVRL ADGTQLMLRP VLPGDRERTV HGHIQFSGET
LYRRFMSARV PSPALMHYLS EVDYVDHFVW VVTDGSDPVA DARFVRDETD PTVAEIAFTV
ADAYQGRGIG SFLIGALSVA ARVDGVERFA ARMLSDNVPM RTIMDRYGAV WQREDVGVIT
TMIDVPGPGE LSLGREMVDQ INRVARQVIE AVG
