PAPA1_MYCTU
ID PAPA1_MYCTU Reviewed; 511 AA.
AC P9WIK9; L0TDN6; O07799; Q7D4T1;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=2'-acyl-2-O-sulfo-trehalose (hydroxy)phthioceranyltransferase PapA1 {ECO:0000305};
DE EC=2.3.1.283 {ECO:0000269|PubMed:17592143, ECO:0000269|PubMed:22194604};
DE AltName: Full=Polyketide synthase-associated protein A1;
DE AltName: Full=SL659 acyltransferase PapA1 {ECO:0000305};
GN Name=papA1; OrderedLocusNames=Rv3824c;
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 REGULATION BY PHOP/PHOR.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16573683; DOI=10.1111/j.1365-2958.2006.05102.x;
RA Walters S.B., Dubnau E., Kolesnikova I., Laval F., Daffe M., Smith I.;
RT "The Mycobacterium tuberculosis PhoPR two-component system regulates genes
RT essential for virulence and complex lipid biosynthesis.";
RL Mol. Microbiol. 60:312-330(2006).
RN [3]
RP FUNCTION AS AN ACYLTRANSFERASE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP HIS-171 AND ASP-175.
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 [4]
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 [5]
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 [6]
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-2'-
CC palmitate (SL659) by adding the (hydroxy)phthioceranoyl group at the
CC 3'-position to yield the diacylated intermediate 2-palmitoyl-3-(C43)-
CC phthioceranyl-alpha, alpha'-D-trehalose-2'-sulfate (SL1278)
CC (PubMed:17592143, PubMed:22194604). {ECO:0000269|PubMed:17259623,
CC ECO:0000269|PubMed:17592143, ECO:0000269|PubMed:22194604}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (hydroxy)phthioceranyl-[(hydroxy)phthioceranic acid
CC synthase] + 2'-palmitoyl/stearoyl-2-O-sulfo-alpha,alpha-trehalose = a
CC 3'-(hydroxy)phthioceranyl-2'-palmitoyl/stearoyl-2-O-sulfo-
CC alpha,alpha-trehalose + holo-[(hydroxy)phthioceranic acid synthase].;
CC EC=2.3.1.283; Evidence={ECO:0000269|PubMed:17592143,
CC ECO:0000269|PubMed:22194604};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=332 uM for trehalose-2-sulfate-2'-palmitate
CC {ECO:0000269|PubMed:17592143};
CC Note=kcat is 0.12 min(-1) with trehalose-2-sulfate-2'-palmitate as
CC substrate. {ECO:0000269|PubMed:17592143};
CC -!- INDUCTION: Up-regulated by the PhoP/PhoR two-component system.
CC {ECO:0000269|PubMed:16573683}.
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; CCP46653.1; -; Genomic_DNA.
DR PIR; D70522; D70522.
DR RefSeq; NP_218341.1; NC_000962.3.
DR RefSeq; WP_003899711.1; NZ_NVQJ01000022.1.
DR AlphaFoldDB; P9WIK9; -.
DR SMR; P9WIK9; -.
DR STRING; 83332.Rv3824c; -.
DR PaxDb; P9WIK9; -.
DR DNASU; 886156; -.
DR GeneID; 886156; -.
DR KEGG; mtu:Rv3824c; -.
DR TubercuList; Rv3824c; -.
DR eggNOG; COG1020; Bacteria.
DR OMA; AEIHLMY; -.
DR PhylomeDB; P9WIK9; -.
DR BioCyc; MetaCyc:G185E-8120-MON; -.
DR BRENDA; 2.3.1.283; 3445.
DR SABIO-RK; P9WIK9; -.
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..511
FT /note="2'-acyl-2-O-sulfo-trehalose
FT (hydroxy)phthioceranyltransferase PapA1"
FT /id="PRO_0000314658"
FT MUTAGEN 171
FT /note="H->A: Loss of sulfolipid-1 (SL-1) production."
FT /evidence="ECO:0000269|PubMed:17259623"
FT MUTAGEN 175
FT /note="D->A: Loss of sulfolipid-1 (SL-1) production."
FT /evidence="ECO:0000269|PubMed:17259623"
SQ SEQUENCE 511 AA; 56128 MW; 07D7766EF181C4E5 CRC64;
MRIGPVELSA VKDWDPAPGV LVSWHPTPAS CAKALAAPVS AVPPSYVQAR QIRSFSEQAA
RGLDHSRLLI ASVEVFGHCD LRAMTYVINA HLRRHDTYRS WFELRDTDHI VRHSIADPAD
IEFVPTTHGE MTSADLRQHI VATPDSLHWD CFSFGVIQRA DSFTFYASID HLHADGQFVG
VGLMEFQSMY TALIMGEPPI GLSEAGSYVD FCVRQHEYTS ALTVDSPEVR AWIDFAEINN
GTFPEFPLPL GDPSVRCGGD LLSMMLMDEQ QTQRFESACM AANARFIGGM LACIAIAIHE
LTGADTYFGI TPKDIRTPAD LMTQGWFTGQ IPVTVPVAGL SFNEIARIAQ TSFDTGADLA
KVPFERVVEL SPSLRRPQPL FSLVNFFDAQ VGPLSAVTKL FEGLNVGTYS DGRVTYPLST
MVGRFDETAA SVLFPDNPVA RESVTAYLRA IRSVCMRIAN GGTAERVGNV VALSPGRRNN
IERMTWRSCR AGDFIDICNL KVANVTVDRE A
