LSPA_STAA3
ID LSPA_STAA3 Reviewed; 163 AA.
AC Q2FHP2;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Lipoprotein signal peptidase {ECO:0000255|HAMAP-Rule:MF_00161, ECO:0000303|PubMed:31919415};
DE EC=3.4.23.36 {ECO:0000255|HAMAP-Rule:MF_00161, ECO:0000269|PubMed:31919415};
DE AltName: Full=LspMrs {ECO:0000303|PubMed:31919415};
DE AltName: Full=Prolipoprotein signal peptidase {ECO:0000255|HAMAP-Rule:MF_00161};
DE AltName: Full=Signal peptidase II {ECO:0000255|HAMAP-Rule:MF_00161};
DE Short=SPase II {ECO:0000255|HAMAP-Rule:MF_00161};
GN Name=lspA {ECO:0000255|HAMAP-Rule:MF_00161, ECO:0000303|PubMed:31919415};
GN OrderedLocusNames=SAUSA300_1089;
OS Staphylococcus aureus (strain USA300).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=367830;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=USA300;
RX PubMed=16517273; DOI=10.1016/s0140-6736(06)68231-7;
RA Diep B.A., Gill S.R., Chang R.F., Phan T.H., Chen J.H., Davidson M.G.,
RA Lin F., Lin J., Carleton H.A., Mongodin E.F., Sensabaugh G.F.,
RA Perdreau-Remington F.;
RT "Complete genome sequence of USA300, an epidemic clone of community-
RT acquired meticillin-resistant Staphylococcus aureus.";
RL Lancet 367:731-739(2006).
RN [2] {ECO:0007744|PDB:6RYO, ECO:0007744|PDB:6RYP}
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) IN COMPLEXES WITH GLOBOMYCIN AND
RP MYXOVIRESCIN, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TOPOLOGY, DISRUPTION
RP PHENOTYPE, BIOTECHNOLOGY, MUTAGENESIS OF ASN-52; GLY-54; ARG-110; ASP-118;
RP ASN-133 AND ASP-136, AND ACTIVE SITES.
RC STRAIN=USA300 / LAC;
RX PubMed=31919415; DOI=10.1038/s41467-019-13724-y;
RA Olatunji S., Yu X., Bailey J., Huang C.Y., Zapotoczna M., Bowen K.,
RA Remskar M., Mueller R., Scanlan E.M., Geoghegan J.A., Olieric V.,
RA Caffrey M.;
RT "Structures of lipoprotein signal peptidase II from Staphylococcus aureus
RT complexed with antibiotics globomycin and myxovirescin.";
RL Nat. Commun. 11:140-140(2020).
CC -!- FUNCTION: This protein specifically catalyzes the removal of signal
CC peptides from prolipoproteins. {ECO:0000255|HAMAP-Rule:MF_00161,
CC ECO:0000269|PubMed:31919415}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of signal peptides from bacterial membrane
CC prolipoproteins. Hydrolyzes -Xaa-Yaa-Zaa-|-(S,diacylglyceryl)Cys-, in
CC which Xaa is hydrophobic (preferably Leu), and Yaa (Ala or Ser) and
CC Zaa (Gly or Ala) have small, neutral side chains.; EC=3.4.23.36;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00161,
CC ECO:0000269|PubMed:31919415};
CC -!- ACTIVITY REGULATION: Inhibited by the antibiotics globomycin and
CC myxovirescin. They act by blocking the catalytic dyad.
CC {ECO:0000269|PubMed:31919415}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=47 uM for P.aeruginosa inhibitor of cysteine peptidase
CC {ECO:0000269|PubMed:31919415};
CC Vmax=2.5 nmol/min/mg enzyme with P.aeruginosa inhibitor of cysteine
CC peptidase as substrate {ECO:0000269|PubMed:31919415};
CC -!- PATHWAY: Protein modification; lipoprotein biosynthesis (signal peptide
CC cleavage). {ECO:0000255|HAMAP-Rule:MF_00161}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255|HAMAP-Rule:MF_00161,
CC ECO:0000269|PubMed:31919415}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_00161, ECO:0000269|PubMed:31919415}.
CC -!- DISRUPTION PHENOTYPE: Mutant in strain LAC grows similarly to wild-type
CC in rich laboratory media, but has a reduced ability to survive in whole
CC human blood. {ECO:0000269|PubMed:31919415}.
CC -!- BIOTECHNOLOGY: LspA is an ideal target for anti-infective agents as it
CC is required for the survival of MRSA under physiologically relevant
CC conditions in human blood. {ECO:0000269|PubMed:31919415}.
CC -!- SIMILARITY: Belongs to the peptidase A8 family. {ECO:0000255|HAMAP-
CC Rule:MF_00161}.
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DR EMBL; CP000255; ABD21210.1; -; Genomic_DNA.
DR RefSeq; WP_000549207.1; NZ_CP027476.1.
DR PDB; 6RYO; X-ray; 1.92 A; A=1-163.
DR PDB; 6RYP; X-ray; 2.30 A; A=1-163.
DR PDBsum; 6RYO; -.
DR PDBsum; 6RYP; -.
DR AlphaFoldDB; Q2FHP2; -.
DR SMR; Q2FHP2; -.
DR EnsemblBacteria; ABD21210; ABD21210; SAUSA300_1089.
DR KEGG; saa:SAUSA300_1089; -.
DR HOGENOM; CLU_083252_3_0_9; -.
DR OMA; NRWYFPA; -.
DR UniPathway; UPA00665; -.
DR Proteomes; UP000001939; 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:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR HAMAP; MF_00161; LspA; 1.
DR InterPro; IPR001872; Peptidase_A8.
DR PANTHER; PTHR33695; PTHR33695; 1.
DR Pfam; PF01252; Peptidase_A8; 1.
DR PRINTS; PR00781; LIPOSIGPTASE.
DR TIGRFAMs; TIGR00077; lspA; 1.
DR PROSITE; PS00855; SPASE_II; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aspartyl protease; Cell membrane; Hydrolase; Membrane;
KW Protease; Transmembrane; Transmembrane helix.
FT CHAIN 1..163
FT /note="Lipoprotein signal peptidase"
FT /id="PRO_0000289433"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:31919415,
FT ECO:0007744|PDB:6RYO"
FT TRANSMEM 7..25
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:31919415,
FT ECO:0007744|PDB:6RYO"
FT TOPO_DOM 26..62
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:31919415,
FT ECO:0007744|PDB:6RYO"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00161,
FT ECO:0000269|PubMed:31919415, ECO:0007744|PDB:6RYO"
FT TOPO_DOM 84..89
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:31919415,
FT ECO:0007744|PDB:6RYO"
FT TRANSMEM 90..112
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:31919415,
FT ECO:0007744|PDB:6RYO"
FT TOPO_DOM 113..133
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:31919415,
FT ECO:0007744|PDB:6RYO"
FT TRANSMEM 134..151
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:31919415,
FT ECO:0007744|PDB:6RYO"
FT TOPO_DOM 152..163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:31919415,
FT ECO:0007744|PDB:6RYO"
FT ACT_SITE 118
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00161,
FT ECO:0000305|PubMed:31919415"
FT ACT_SITE 136
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00161,
FT ECO:0000305|PubMed:31919415"
FT MUTAGEN 52
FT /note="N->A: Retains 7% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:31919415"
FT MUTAGEN 52
FT /note="N->Q: Retains 71% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:31919415"
FT MUTAGEN 54
FT /note="G->A: Small increase in activity."
FT /evidence="ECO:0000269|PubMed:31919415"
FT MUTAGEN 54
FT /note="G->P: Loss of activity."
FT /evidence="ECO:0000269|PubMed:31919415"
FT MUTAGEN 110
FT /note="R->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:31919415"
FT MUTAGEN 110
FT /note="R->K: Retains 50% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:31919415"
FT MUTAGEN 118
FT /note="D->N: Loss of activity."
FT /evidence="ECO:0000269|PubMed:31919415"
FT MUTAGEN 133
FT /note="N->A,Q: Retains 3% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:31919415"
FT MUTAGEN 136
FT /note="D->N: Loss of activity."
FT /evidence="ECO:0000269|PubMed:31919415"
SQ SEQUENCE 163 AA; 18342 MW; B9D42A904F0BF33F CRC64;
MHKKYFIGTS ILIAVFVVIF DQVTKYIIAT TMKIGDSFEV IPHFLNITSH RNNGAAWGIL
SGKMTFFFII TIIILIALVY FFIKDAQYNL FMQVAISLLF AGALGNFIDR ILTGEVVDFI
DTNIFGYDFP IFNIADSSLT IGVILIIIAL LKDTSNKKEK EVK
