FABD_MYCTU
ID FABD_MYCTU Reviewed; 302 AA.
AC P9WNG5; L0TAL7; P63458; Q10501;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 36.
DE RecName: Full=Malonyl CoA-acyl carrier protein transacylase;
DE Short=MCT;
DE EC=2.3.1.39;
GN Name=fabD; OrderedLocusNames=Rv2243; ORFNames=MTCY427.24;
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 PROTEASOME SUBSTRATE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17082771; DOI=10.1038/sj.emboj.7601405;
RA Pearce M.J., Arora P., Festa R.A., Butler-Wu S.M., Gokhale R.S.,
RA Darwin K.H.;
RT "Identification of substrates of the Mycobacterium tuberculosis
RT proteasome.";
RL EMBO J. 25:5423-5432(2006).
RN [3]
RP PUPYLATION AT LYS-173, MUTAGENESIS OF LYS-173, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18832610; DOI=10.1126/science.1163885;
RA Pearce M.J., Mintseris J., Ferreyra J., Gygi S.P., Darwin K.H.;
RT "Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium
RT tuberculosis.";
RL Science 322:1104-1107(2008).
RN [4]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [5]
RP PUPYLATION AT LYS-173, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20066036; DOI=10.1371/journal.pone.0008589;
RA Festa R.A., McAllister F., Pearce M.J., Mintseris J., Burns K.E.,
RA Gygi S.P., Darwin K.H.;
RT "Prokaryotic ubiquitin-like protein (Pup) proteome of Mycobacterium
RT tuberculosis.";
RL PLoS ONE 5:E8589-E8589(2010).
RN [6]
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).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=holo-[ACP] + malonyl-CoA = CoA + malonyl-[ACP];
CC Xref=Rhea:RHEA:41792, Rhea:RHEA-COMP:9623, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449; EC=2.3.1.39;
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC -!- PTM: Pupylated at Lys-173 by the prokaryotic ubiquitin-like protein
CC Pup, which leads to its degradation by the proteasome.
CC {ECO:0000269|PubMed:18832610, ECO:0000269|PubMed:20066036}.
CC -!- MISCELLANEOUS: Was identified as a natural substrate of the
CC M.tuberculosis proteasome.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the FabD family. {ECO:0000305}.
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DR EMBL; AL123456; CCP45023.1; -; Genomic_DNA.
DR PIR; G70778; G70778.
DR RefSeq; NP_216759.1; NC_000962.3.
DR RefSeq; WP_003411559.1; NZ_NVQJ01000008.1.
DR PDB; 2QC3; X-ray; 2.30 A; A=1-302.
DR PDB; 2QJ3; X-ray; 3.00 A; A/B=1-302.
DR PDBsum; 2QC3; -.
DR PDBsum; 2QJ3; -.
DR AlphaFoldDB; P9WNG5; -.
DR SMR; P9WNG5; -.
DR STRING; 83332.Rv2243; -.
DR SwissLipids; SLP:000000965; -.
DR PaxDb; P9WNG5; -.
DR GeneID; 888769; -.
DR KEGG; mtu:Rv2243; -.
DR TubercuList; Rv2243; -.
DR eggNOG; COG0331; Bacteria.
DR OMA; AANYNCP; -.
DR PhylomeDB; P9WNG5; -.
DR BRENDA; 2.3.1.39; 3445.
DR BRENDA; 4.1.2.25; 3445.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005835; C:fatty acid synthase complex; IDA:MTBBASE.
DR GO; GO:0004314; F:[acyl-carrier-protein] S-malonyltransferase activity; IDA:MTBBASE.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IDA:MTBBASE.
DR Gene3D; 3.40.366.10; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Fatty acid biosynthesis;
KW Fatty acid metabolism; Isopeptide bond; Lipid biosynthesis;
KW Lipid metabolism; Reference proteome; Transferase; Ubl conjugation.
FT CHAIN 1..302
FT /note="Malonyl CoA-acyl carrier protein transacylase"
FT /id="PRO_0000194218"
FT ACT_SITE 91
FT /evidence="ECO:0000250"
FT ACT_SITE 194
FT /evidence="ECO:0000250"
FT CROSSLNK 173
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-Cter in protein Pup)"
FT /evidence="ECO:0000269|PubMed:18832610,
FT ECO:0000269|PubMed:20066036"
FT MUTAGEN 173
FT /note="K->A: Nearly abolishes pupylation and dramatically
FT stabilizes this proteasome substrate in wild-type
FT mycobacteria."
FT /evidence="ECO:0000269|PubMed:18832610"
FT STRAND 1..6
FT /evidence="ECO:0007829|PDB:2QC3"
FT TURN 14..22
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 26..36
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 41..46
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 56..76
FT /evidence="ECO:0007829|PDB:2QC3"
FT TURN 77..82
FT /evidence="ECO:0007829|PDB:2QC3"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 93..100
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 106..124
FT /evidence="ECO:0007829|PDB:2QC3"
FT STRAND 129..137
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 139..148
FT /evidence="ECO:0007829|PDB:2QC3"
FT STRAND 152..158
FT /evidence="ECO:0007829|PDB:2QC3"
FT STRAND 161..167
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 168..176
FT /evidence="ECO:0007829|PDB:2QC3"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 196..201
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 202..210
FT /evidence="ECO:0007829|PDB:2QC3"
FT STRAND 218..222
FT /evidence="ECO:0007829|PDB:2QC3"
FT TURN 224..226
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 233..242
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 250..259
FT /evidence="ECO:0007829|PDB:2QC3"
FT STRAND 262..267
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 274..281
FT /evidence="ECO:0007829|PDB:2QC3"
FT STRAND 287..289
FT /evidence="ECO:0007829|PDB:2QC3"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:2QC3"
FT TURN 296..300
FT /evidence="ECO:0007829|PDB:2QC3"
SQ SEQUENCE 302 AA; 30788 MW; BB7BCD8217FC66C8 CRC64;
MIALLAPGQG SQTEGMLSPW LQLPGAADQI AAWSKAADLD LARLGTTAST EEITDTAVAQ
PLIVAATLLA HQELARRCVL AGKDVIVAGH SVGEIAAYAI AGVIAADDAV ALAATRGAEM
AKACATEPTG MSAVLGGDET EVLSRLEQLD LVPANRNAAG QIVAAGRLTA LEKLAEDPPA
KARVRALGVA GAFHTEFMAP ALDGFAAAAA NIATADPTAT LLSNRDGKPV TSAAAAMDTL
VSQLTQPVRW DLCTATLREH TVTAIVEFPP AGTLSGIAKR ELRGVPARAV KSPADLDELA
NL
