MPRF_STAA8
ID MPRF_STAA8 Reviewed; 840 AA.
AC Q2G2M2;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Phosphatidylglycerol lysyltransferase;
DE EC=2.3.2.3;
DE AltName: Full=Lysylphosphatidylglycerol synthase;
DE Short=LPG synthase;
DE AltName: Full=Multiple peptide resistance factor;
GN Name=mprF; OrderedLocusNames=SAOUHSC_01359;
OS Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=93061;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISRUPTION PHENOTYPE, AND HOST DEFENSE
RP PEPTIDES RESISTANCE.
RX PubMed=11342591; DOI=10.1084/jem.193.9.1067;
RA Peschel A., Jack R.W., Otto M., Collins L.V., Staubitz P., Nicholson G.,
RA Kalbacher H., Nieuwenhuizen W.F., Jung G., Tarkowski A., van Kessel K.P.M.,
RA van Strijp J.A.G.;
RT "Staphylococcus aureus resistance to human defensins and evasion of
RT neutrophil killing via the novel virulence factor MprF is based on
RT modification of membrane lipids with L-lysine.";
RL J. Exp. Med. 193:1067-1076(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NCTC 8325 / PS 47;
RA Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J.;
RT "The Staphylococcus aureus NCTC 8325 genome.";
RL (In) Fischetti V., Novick R., Ferretti J., Portnoy D., Rood J. (eds.);
RL Gram positive pathogens, 2nd edition, pp.381-412, ASM Press, Washington
RL D.C. (2006).
RN [3]
RP HOST DEFENSE PEPTIDES RESISTANCE.
RX PubMed=12496209; DOI=10.1128/iai.71.1.546-549.2003;
RA Kristian S.A., Duerr M., van Strijp J.A.G., Neumeister B., Peschel A.;
RT "MprF-mediated lysinylation of phospholipids in Staphylococcus aureus leads
RT to protection against oxygen-independent neutrophil killing.";
RL Infect. Immun. 71:546-549(2003).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=14769468; DOI=10.1016/s0378-1097(03)00921-2;
RA Staubitz P., Neumann H., Schneider T., Wiedemann I., Peschel A.;
RT "MprF-mediated biosynthesis of lysylphosphatidylglycerol, an important
RT determinant in staphylococcal defensin resistance.";
RL FEMS Microbiol. Lett. 231:67-71(2004).
RN [5]
RP FUNCTION, KINETIC PARAMETERS, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=14702396; DOI=10.1099/mic.0.26706-0;
RA Oku Y., Kurokawa K., Ichihashi N., Sekimizu K.;
RT "Characterization of the Staphylococcus aureus mprF gene, involved in
RT lysinylation of phosphatidylglycerol.";
RL Microbiology 150:45-51(2004).
CC -!- FUNCTION: Catalyzes the transfer of a lysyl group from L-lysyl-
CC tRNA(Lys) to membrane-bound phosphatidylglycerol (PG), which produces
CC lysylphosphatidylglycerol (LPG), a major component of the bacterial
CC membrane with a positive net charge. LPG synthesis contributes to
CC bacterial virulence as it is involved in the resistance mechanism
CC against cationic antimicrobial peptides (CAMP) produces by the host's
CC immune system (defensins, cathelicidins) and by the competing
CC microorganisms (bacteriocins). In fact, the modification of anionic
CC phosphatidylglycerol with positively charged L-lysine results in
CC repulsion of the peptides. Consequently, MprF is shown to affect
CC resistance and susceptibility to moenomycin and vancomycin, resistance
CC to human defensins (HNP1-3) and evasion of oxygen-independent
CC neutrophil killing and susceptibility to methicillin, oxacillin,
CC bacitracin, gentamicin, beta-lactams and synthetic peptides (hBD3,
CC CAP18) and other cationic antimicrobial peptides.
CC {ECO:0000269|PubMed:14702396, ECO:0000269|PubMed:14769468}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol) + L-lysyl-
CC tRNA(Lys) = 1,2-diacyl-sn-glycero-3-phospho-1'-(3'-O-L-lysyl)-sn-
CC glycerol + tRNA(Lys); Xref=Rhea:RHEA:10668, Rhea:RHEA-COMP:9696,
CC Rhea:RHEA-COMP:9697, ChEBI:CHEBI:64716, ChEBI:CHEBI:75792,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78529; EC=2.3.2.3;
CC Evidence={ECO:0000269|PubMed:14769468};
CC -!- ACTIVITY REGULATION: Inhibited by cadaverin or RNase A.
CC {ECO:0000269|PubMed:14769468}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.9 uM for L-lysyl-tRNA {ECO:0000269|PubMed:14702396};
CC KM=56 uM for phosphatidylglycerol {ECO:0000269|PubMed:14702396};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14702396};
CC Multi-pass membrane protein {ECO:0000269|PubMed:14702396}.
CC -!- DISRUPTION PHENOTYPE: Strains lacking this gene do not have a
CC detectable amount of LPG in their membrane lipids. They are also more
CC susceptible to defensin and have a higher affinity for cationic
CC peptides. {ECO:0000269|PubMed:11342591, ECO:0000269|PubMed:14702396}.
CC -!- SIMILARITY: Belongs to the LPG synthase family. {ECO:0000305}.
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DR EMBL; AF145699; AAK58115.1; -; Genomic_DNA.
DR EMBL; CP000253; ABD30454.1; -; Genomic_DNA.
DR RefSeq; WP_001071135.1; NZ_LS483365.1.
DR RefSeq; YP_499886.1; NC_007795.1.
DR AlphaFoldDB; Q2G2M2; -.
DR SMR; Q2G2M2; -.
DR STRING; 1280.SAXN108_1376; -.
DR EnsemblBacteria; ABD30454; ABD30454; SAOUHSC_01359.
DR GeneID; 3920064; -.
DR KEGG; sao:SAOUHSC_01359; -.
DR PATRIC; fig|93061.5.peg.1243; -.
DR eggNOG; COG0392; Bacteria.
DR eggNOG; COG2898; Bacteria.
DR HOGENOM; CLU_008255_7_1_9; -.
DR OMA; WEPRYMA; -.
DR BioCyc; MetaCyc:MON-7721; -.
DR BRENDA; 2.3.2.3; 3352.
DR PHI-base; PHI:7738; -.
DR PRO; PR:Q2G2M2; -.
DR Proteomes; UP000008816; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016755; F:aminoacyltransferase activity; IBA:GO_Central.
DR GO; GO:0050071; F:lysyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0055091; P:phospholipid homeostasis; IBA:GO_Central.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR022791; L-PG_synthase/AglD.
DR InterPro; IPR024320; LPG_synthase_C.
DR Pfam; PF09924; LPG_synthase_C; 1.
DR Pfam; PF03706; LPG_synthase_TM; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR TIGRFAMs; TIGR00374; TIGR00374; 1.
PE 1: Evidence at protein level;
KW Antibiotic resistance; Cell membrane; Lipid metabolism; Membrane;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix;
KW Virulence.
FT CHAIN 1..840
FT /note="Phosphatidylglycerol lysyltransferase"
FT /id="PRO_0000247953"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..52
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 53..73
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 74..89
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 90..110
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 111..128
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 129..149
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 150..161
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 162..182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..200
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..229
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 251..271
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..292
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 293..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..369
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 370..390
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 391..394
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 395..415
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 416..436
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 437..450
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 451..471
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 472..489
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 490..510
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 511..840
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
SQ SEQUENCE 840 AA; 96866 MW; 611F18831F42A6AD CRC64;
MNQEVKNKIF SILKITFATA LFIFVAITLY RELSGINFKD TLVEFSKINR MSLVLLFIGG
GASLVILSMY DVILSRALKM DISLGKVLRV SYIINALNAI VGFGGFIGAG VRAMVYKNYT
HDKKKLVHFI SLILISMLTG LSLLSLLIVF HVFDASLILD KITWVRWVLY VVSFFLPLFI
IYSMVRPPDK NNRFVGLYCT LVSCVEWLAA AVVLYFCGVI VDAHVSFMSF IAIFIIAALS
GLVSFIPGGF GAFDLVVLLG FKTLGVPEEK VLLMLLLYRF AYYFVPVIIA LILSSFEFGT
SAKKYIEGSK YFIPAKDVTS FLMSYQKDII AKIPSLSLAI LVFFTSMIFF VNNLTIVYDA
LYDGNHLTYY ILLAIHTSAC LLLLLNVVGI YKQSRRAIIF AMISILLITV ATFFTYASYI
LITWLAIIFV LLIVAFRRAR RLKRPVRMRN IVAMLLFSLF ILYVNHIFIA GTLYALDIYT
IEMHTSVLRY YFWLTILIIA IIIGMIAWLF DYQFSKVRIS SKIEDCEEII NQYGGNYLSH
LIYSGDKQFF TNENKTAFLM YRYKASSLVV LGDPLGDENA FDELLEAFYN YAEYLGYDVI
FYQVTDQHMP LYHNFGNQFF KLGEEAIIDL TQFSTSGKKR RGFRATLNKF DELNISFEII
EPPFSTEFIN ELQHVSDLWL DNRQEMHFSV GEFNEEYLSK APIGVMRNEE NEVIAFCSLM
PTYFNDAISV DLIRWLPELD LPLMDGLYLH MLLWSKEQGY TKFNMGMATL SNVGQLHYSY
LRERLAGRVF EHFNGLYRFQ GLRRYKSKYN PNWEPRFLVY RKDNSLWESL SKVMRVIRHK
