PAPA2_MYCTU
ID PAPA2_MYCTU Reviewed; 468 AA.
AC P9WIK7; L0TDW1; Q79F94; Q7D4T4;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Trehalose-2-sulfate acyltransferase PapA2 {ECO:0000305};
DE EC=2.3.1.288 {ECO:0000269|PubMed:17592143, ECO:0000269|PubMed:22194604};
DE AltName: Full=2-O-sulfo trehalose long-chain-acyltransferase {ECO:0000305};
DE AltName: Full=Polyketide synthase-associated protein A2;
GN Name=papA2; OrderedLocusNames=Rv3820c;
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 AS AN ACYLTRANSFERASE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP HIS-166 AND ASP-170.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17259623; DOI=10.1099/mic.0.2006/003103-0;
RA Bhatt K., Gurcha S.S., Bhatt A., Besra G.S., Jacobs W.R. Jr.;
RT "Two polyketide-synthase-associated acyltransferases are required for
RT sulfolipid biosynthesis in Mycobacterium tuberculosis.";
RL Microbiology 153:513-520(2007).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17592143; DOI=10.1073/pnas.0611649104;
RA Kumar P., Schelle M.W., Jain M., Lin F.L., Petzold C.J., Leavell M.D.,
RA Leary J.A., Cox J.S., Bertozzi C.R.;
RT "PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the
RT Mycobacterium tuberculosis virulence factor sulfolipid-1.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:11221-11226(2007).
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 FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22194604; DOI=10.1074/jbc.m111.315473;
RA Seeliger J.C., Holsclaw C.M., Schelle M.W., Botyanszki Z., Gilmore S.A.,
RA Tully S.E., Niederweis M., Cravatt B.F., Leary J.A., Bertozzi C.R.;
RT "Elucidation and chemical modulation of sulfolipid-1 biosynthesis in
RT Mycobacterium tuberculosis.";
RL J. Biol. Chem. 287:7990-8000(2012).
CC -!- FUNCTION: Required for the biosynthesis of sulfolipid-1 (SL-1), a major
CC mycobacterial cell wall lipid (PubMed:17259623, PubMed:17592143,
CC PubMed:22194604). Catalyzes the acylation of trehalose-2-sulfate by
CC adding the palmitoyl group at the 2'-position to yield the intermediate
CC trehalose-2-sulfate-2'-palmitate (SL659) (PubMed:17592143,
CC PubMed:22194604). {ECO:0000269|PubMed:17259623,
CC ECO:0000269|PubMed:17592143, ECO:0000269|PubMed:22194604}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-O-sulfo-alpha,alpha-trehalose + hexadecanoyl-CoA = 2-O-
CC sulfo-2'-O-hexadecanoyl-alpha,alpha-trehalose + CoA;
CC Xref=Rhea:RHEA:44060, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:60091, ChEBI:CHEBI:60092; EC=2.3.1.288;
CC Evidence={ECO:0000269|PubMed:17592143, ECO:0000269|PubMed:22194604};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44061;
CC Evidence={ECO:0000269|PubMed:17592143, ECO:0000269|PubMed:22194604};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.5 mM for trehalose-2-sulfate {ECO:0000269|PubMed:17592143};
CC KM=5.96 uM for palmitoyl-CoA {ECO:0000269|PubMed:17592143};
CC Note=kcat is 0.4 min(-1) with trehalose-2-sulfate as substrate. kcat
CC is 0.19 min(-1) with palmitoyl-CoA as substrate.
CC {ECO:0000269|PubMed:17592143};
CC -!- DISRUPTION PHENOTYPE: Null mutant does not produce SL-1
CC (PubMed:17259623, PubMed:17592143). Disruption of the gene does not
CC alter the virulence of M.tuberculosis in mice (PubMed:17592143).
CC {ECO:0000269|PubMed:17259623, ECO:0000269|PubMed:17592143}.
CC -!- SIMILARITY: Belongs to the PapA acyltransferase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46649.1; -; Genomic_DNA.
DR PIR; H70521; H70521.
DR RefSeq; WP_003899707.1; NZ_NVQJ01000022.1.
DR RefSeq; YP_178020.1; NC_000962.3.
DR AlphaFoldDB; P9WIK7; -.
DR SMR; P9WIK7; -.
DR STRING; 83332.Rv3820c; -.
DR SwissLipids; SLP:000001029; -.
DR PaxDb; P9WIK7; -.
DR DNASU; 886140; -.
DR GeneID; 886140; -.
DR KEGG; mtu:Rv3820c; -.
DR TubercuList; Rv3820c; -.
DR eggNOG; COG1020; Bacteria.
DR OMA; CMWVNRF; -.
DR PhylomeDB; P9WIK7; -.
DR BioCyc; MetaCyc:G185E-8116-MON; -.
DR BRENDA; 2.3.1.288; 3445.
DR SABIO-RK; P9WIK7; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IDA:MTBBASE.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0046506; P:sulfolipid biosynthetic process; IMP:MTBBASE.
DR Gene3D; 3.30.559.10; -; 1.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR Pfam; PF00668; Condensation; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Cell wall biogenesis/degradation; Lipid biosynthesis;
KW Lipid metabolism; Reference proteome; Transferase.
FT CHAIN 1..468
FT /note="Trehalose-2-sulfate acyltransferase PapA2"
FT /id="PRO_0000314662"
FT MUTAGEN 166
FT /note="H->A: Loss of sulfolipid-1 (SL-1) production."
FT /evidence="ECO:0000269|PubMed:17259623"
FT MUTAGEN 170
FT /note="D->A: Loss of sulfolipid-1 (SL-1) production."
FT /evidence="ECO:0000269|PubMed:17259623"
SQ SEQUENCE 468 AA; 52150 MW; 9163239A6400DED9 CRC64;
MFSITTLRDW TPDPGSIICW HASPTAKAKA RQAPISEVPP SYQQAQHLRR YRDHVARGLD
MSRLMIFTWD LPGRCNIRAM NYAINAHLRR HDTYHSWFEF DNAEHIVRHT IADPADIEVV
QAEHQNMTSA ELRHHIATPQ PLQWDCFLFG IIQSDDHFTF YASIAHLCVD PMIVGVLFIE
IHMMYSALVG GDPPIELPPA GRYDDHCVRQ YADTAALTLD SARVRRWVEF AANNDGTLPH
FPLPLGDLSV PHTGKLLTET LMDEQQGERF EAACVAAGAR FSGGVFACAA LAERELTNCE
TFDVVTTTDT RRTPTELRTT GWFTGLVPIT VPVASGLFDS AARVAQISFD SGKDLATVPF
DRVLELARPE TGLRPPRPGN FVMSFLDASI APLSTVANSD LNFRIYDEGR VSHQVSMWVN
RYQHQTTVTV LFPDNPIASE SVANYIAAMK SIYIRTADGT LATLKPGT
