MBTM_MYCS2
ID MBTM_MYCS2 Reviewed; 526 AA.
AC A0QUA1; I7FIE2;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 25-MAY-2022, entry version 98.
DE RecName: Full=Medium/long-chain-fatty-acid--[acyl-carrier-protein] ligase MbtM {ECO:0000305};
DE EC=6.2.1.20 {ECO:0000269|PubMed:23935107};
DE EC=6.2.1.47 {ECO:0000269|PubMed:23935107};
DE AltName: Full=Fatty acyl-[acyl-carrier-protein] synthetase {ECO:0000305};
DE Short=Fatty acyl-ACP synthetase {ECO:0000305};
DE AltName: Full=Mycobactin fatty acyl-AMP ligase {ECO:0000303|PubMed:23935107};
DE AltName: Full=Mycobactin synthetase protein M {ECO:0000305};
GN Name=mbtM {ECO:0000303|PubMed:23935107};
GN Synonyms=fadD33 {ECO:0000303|PubMed:23935107};
GN OrderedLocusNames=MSMEG_2131 {ECO:0000312|EMBL:ABK75882.1},
GN MSMEI_2082 {ECO:0000312|EMBL:AFP38553.1};
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, ACETYLATION AT LYS-260 AND LYS-511,
RP AND MUTAGENESIS OF LYS-260 AND LYS-511.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=23935107; DOI=10.1074/jbc.m113.495549;
RA Vergnolle O., Xu H., Blanchard J.S.;
RT "Mechanism and regulation of mycobactin fatty acyl-AMP ligase FadD33.";
RL J. Biol. Chem. 288:28116-28125(2013).
CC -!- FUNCTION: Activates lipidic moieties required for mycobactin
CC biosynthesis (PubMed:23935107). Converts medium- to long-chain
CC aliphatic fatty acids into acyl adenylate, which is further transferred
CC on to the phosphopantetheine arm of the carrier protein MbtL
CC (PubMed:23935107). Shows a strong preference for palmitic acid (C16)
CC and cannot use short-chain fatty acids (PubMed:23935107). Proceeds via
CC a Bi Uni Uni Bi ping-pong mechanism. During the first half-reaction
CC (adenylation), fatty acid binds first to the free enzyme, followed by
CC ATP and the release of pyrophosphate to form the adenylate
CC intermediate. During the second half-reaction (ligation), holo-MbtL
CC binds to the enzyme followed by the release of products AMP and
CC acylated MbtL (PubMed:23935107). {ECO:0000269|PubMed:23935107}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain fatty acid + ATP + holo-[ACP] = a long-chain
CC fatty acyl-[ACP] + AMP + diphosphate; Xref=Rhea:RHEA:45588,
CC Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:12682, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57560, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:133243, ChEBI:CHEBI:456215; EC=6.2.1.20;
CC Evidence={ECO:0000269|PubMed:23935107};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a medium chain fatty acid + ATP + holo-[ACP] = a medium-chain
CC fatty acyl-[ACP] + AMP + diphosphate; Xref=Rhea:RHEA:50460,
CC Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:12681, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:59558, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:133242, ChEBI:CHEBI:456215; EC=6.2.1.47;
CC Evidence={ECO:0000269|PubMed:23935107};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + hexadecanoate + holo-[ACP] = AMP + diphosphate +
CC hexadecanoyl-[ACP]; Xref=Rhea:RHEA:63628, Rhea:RHEA-COMP:9652,
CC Rhea:RHEA-COMP:9685, ChEBI:CHEBI:7896, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:64479, ChEBI:CHEBI:78483,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:23935107};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63629;
CC Evidence={ECO:0000269|PubMed:23935107};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H(+) + hexadecanoate = diphosphate + hexadecanoyl-AMP;
CC Xref=Rhea:RHEA:43708, ChEBI:CHEBI:7896, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:83627;
CC Evidence={ECO:0000269|PubMed:23935107};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43709;
CC Evidence={ECO:0000269|PubMed:23935107};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-AMP + holo-[ACP] = AMP + H(+) + hexadecanoyl-
CC [ACP]; Xref=Rhea:RHEA:63624, Rhea:RHEA-COMP:9652, Rhea:RHEA-
CC COMP:9685, ChEBI:CHEBI:15378, ChEBI:CHEBI:64479, ChEBI:CHEBI:78483,
CC ChEBI:CHEBI:83627, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:23935107};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63625;
CC Evidence={ECO:0000269|PubMed:23935107};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + dodecanoate + holo-[ACP] = AMP + diphosphate +
CC dodecanoyl-[ACP]; Xref=Rhea:RHEA:63620, Rhea:RHEA-COMP:9644,
CC Rhea:RHEA-COMP:9685, ChEBI:CHEBI:18262, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:64479, ChEBI:CHEBI:65264,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:23935107};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63621;
CC Evidence={ECO:0000269|PubMed:23935107};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + dodecanoate + H(+) = diphosphate + dodecanoyl-AMP;
CC Xref=Rhea:RHEA:43712, ChEBI:CHEBI:15378, ChEBI:CHEBI:18262,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:83623;
CC Evidence={ECO:0000269|PubMed:23935107};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43713;
CC Evidence={ECO:0000269|PubMed:23935107};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-AMP + holo-[ACP] = AMP + dodecanoyl-[ACP] + H(+);
CC Xref=Rhea:RHEA:46504, Rhea:RHEA-COMP:9644, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:64479, ChEBI:CHEBI:65264,
CC ChEBI:CHEBI:83623, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:23935107};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46505;
CC Evidence={ECO:0000269|PubMed:23935107};
CC -!- ACTIVITY REGULATION: Reversibly inactivated by post-translational
CC acetylation by Pat in a cAMP-dependent manner and reactivated by Sir2
CC deacylase. {ECO:0000269|PubMed:23935107}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=129 uM for hexanoic acid {ECO:0000269|PubMed:23935107};
CC KM=121 uM for decanoic acid {ECO:0000269|PubMed:23935107};
CC KM=21 uM for lauric acid {ECO:0000269|PubMed:23935107};
CC KM=1.9 uM for palmitic acid {ECO:0000269|PubMed:23935107};
CC KM=15 uM for ATP {ECO:0000269|PubMed:23935107};
CC KM=106 uM for MbtL-holo {ECO:0000269|PubMed:23935107};
CC Note=kcat is 0.11 min(-1) with hexanoic acid as substrate. kcat is
CC 1.5 min(-1) with decanoic acid as substrate. kcat is 2.4 min(-1) with
CC lauric acid as substrate. kcat is 4.2 min(-1) with palmitic acid as
CC substrate. kcat is 1.3 min(-1) with ATP as substrate. kcat is 2.0
CC min(-1) with MbtL-holo as substrate. {ECO:0000269|PubMed:23935107};
CC -!- PATHWAY: Siderophore biosynthesis; mycobactin biosynthesis.
CC {ECO:0000269|PubMed:23935107}.
CC -!- PTM: Acetylated on Lys-511 and Lys-260 by Pat. Lys-511 is the major
CC acetylation site. Acetylation results in the inactivation of the
CC enzyme. {ECO:0000269|PubMed:23935107}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; CP000480; ABK75882.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP38553.1; -; Genomic_DNA.
DR RefSeq; WP_003893504.1; NZ_SIJM01000021.1.
DR RefSeq; YP_886489.1; NC_008596.1.
DR AlphaFoldDB; A0QUA1; -.
DR SMR; A0QUA1; -.
DR STRING; 246196.MSMEI_2082; -.
DR EnsemblBacteria; ABK75882; ABK75882; MSMEG_2131.
DR EnsemblBacteria; AFP38553; AFP38553; MSMEI_2082.
DR GeneID; 66733556; -.
DR KEGG; msg:MSMEI_2082; -.
DR KEGG; msm:MSMEG_2131; -.
DR PATRIC; fig|246196.19.peg.2105; -.
DR eggNOG; COG0318; Bacteria.
DR OMA; FRWLTWL; -.
DR OrthoDB; 572620at2; -.
DR UniPathway; UPA00011; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008922; F:long-chain fatty acid [acyl-carrier-protein] ligase activity; IEA:UniProtKB-EC.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
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; PF00501; AMP-binding; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Ligase; Nucleotide-binding; Reference proteome.
FT CHAIN 1..526
FT /note="Medium/long-chain-fatty-acid--[acyl-carrier-protein]
FT ligase MbtM"
FT /id="PRO_0000450445"
FT MOD_RES 260
FT /note="N6-acetyllysine; by Pat"
FT /evidence="ECO:0000269|PubMed:23935107"
FT MOD_RES 511
FT /note="N6-acetyllysine; by Pat"
FT /evidence="ECO:0000269|PubMed:23935107"
FT MUTAGEN 260
FT /note="K->A: Still active. Slight decrease in acetylation
FT by Pat. Loss of acetylation; when associated with A-511."
FT /evidence="ECO:0000269|PubMed:23935107"
FT MUTAGEN 511
FT /note="K->A: Loss of activity. Strong decrease in
FT acetylation by Pat. Loss of acetylation; when associated
FT with A-260."
FT /evidence="ECO:0000269|PubMed:23935107"
SQ SEQUENCE 526 AA; 55359 MW; 42041AF2DAC5B71C CRC64;
MNVLSAALTE AMTTSSADLV VFEPETRTWH RHPWGQVHLR AQNVAERIGQ DGSSAVGIVG
EPTVEGVAAI LGALLAGSAV SILPGLVRGA DPDQWADSTL NRFANIGVTT VFSHGSYLEQ
LRTRDSSLVI HDDAEVAHAQ RSTTLELGAP LGEFAVLQGT AGSTGTPRTA QLRPDAVLAN
LRGLAERVGL AGSDIGCSWL PLYHDMGLTF LLSAAVGGTE TWQAPTTAFA SAPFSWVHWL
TESRATLTAA PNMAYGLIGK YSRRLTDVDL SAMRFALNGG EPVDIDGTAR FGTELSRFGF
DPGALSPSYG LAESSCAVTV PVPGVGLKVD EITVTTEAGS STQKLAVLGH AIAGMEVRLQ
PGDEDAGVVD REVGEVEIRG TSMMSGYRGE APLDPGEWFP TGDLGYLTDD GLVICGRKKE
LITVAGRNIF PTEIERIAAR VKGVREGAVV AVGTNERAVR PGLVIAAEFR GPDEAGARSE
VVQRVASECG VVPADVVFLA PGSLPRTSSG KLRRLEVKRQ LEESKG
