LSPA_PSEAE
ID LSPA_PSEAE Reviewed; 169 AA.
AC Q9HVM5;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Lipoprotein signal peptidase {ECO:0000255|HAMAP-Rule:MF_00161, ECO:0000303|PubMed:26912896};
DE EC=3.4.23.36 {ECO:0000255|HAMAP-Rule:MF_00161, ECO:0000269|PubMed:26912896, ECO:0000269|PubMed:31919415};
DE AltName: Full=LspPae {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, ECO:0000303|PubMed:26912896};
DE Short=SPase II {ECO:0000255|HAMAP-Rule:MF_00161};
GN Name=lspA {ECO:0000255|HAMAP-Rule:MF_00161, ECO:0000303|PubMed:26912896};
GN Synonyms=ls; OrderedLocusNames=PA4559;
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
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).
RN [3] {ECO:0007744|PDB:5DIR}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS
RP OF ASP-115; ARG-116; ASP-124 AND ASP-143, AND ACTIVE SITES.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=26912896; DOI=10.1126/science.aad3747;
RA Vogeley L., El Arnaout T., Bailey J., Stansfeld P.J., Boland C.,
RA Caffrey M.;
RT "Structural basis of lipoprotein signal peptidase II action and inhibition
RT by the antibiotic globomycin.";
RL Science 351:876-880(2016).
RN [4] {ECO:0007744|PDB:6FMS}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 2-169, SUBCELLULAR LOCATION, AND
RP TOPOLOGY.
RX PubMed=30272004; DOI=10.1038/s42003-018-0123-6;
RA Huang C.Y., Olieric V., Howe N., Warshamanage R., Weinert T., Panepucci E.,
RA Vogeley L., Basu S., Diederichs K., Caffrey M., Wang M.;
RT "In situ serial crystallography for rapid de novo membrane protein
RT structure determination.";
RL Commun. Biol. 1:124-124(2018).
CC -!- FUNCTION: This protein specifically catalyzes the removal of signal
CC peptides from prolipoproteins. {ECO:0000255|HAMAP-Rule:MF_00161,
CC ECO:0000269|PubMed:26912896, 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:26912896, ECO:0000269|PubMed:31919415};
CC -!- ACTIVITY REGULATION: Inhibited by globomycin.
CC {ECO:0000269|PubMed:26912896, ECO:0000269|PubMed:31919415}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10 uM for inhibitor of cysteine peptidase
CC {ECO:0000269|PubMed:31919415};
CC Vmax=107 nmol/min/mg enzyme with inhibitor of cysteine peptidase as
CC substrate {ECO:0000269|PubMed:31919415};
CC -!- PATHWAY: Protein modification; lipoprotein biosynthesis (signal peptide
CC cleavage). {ECO:0000255|HAMAP-Rule:MF_00161}.
CC -!- SUBUNIT: Monomer in the crystal. {ECO:0000269|PubMed:26912896}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000255|HAMAP-
CC Rule:MF_00161, ECO:0000269|PubMed:26912896,
CC ECO:0000269|PubMed:30272004}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_00161, ECO:0000269|PubMed:26912896,
CC ECO:0000269|PubMed:30272004}.
CC -!- SIMILARITY: Belongs to the peptidase A8 family. {ECO:0000255|HAMAP-
CC Rule:MF_00161}.
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DR EMBL; AE004091; AAG07947.1; -; Genomic_DNA.
DR PIR; A83077; A83077.
DR RefSeq; NP_253249.1; NC_002516.2.
DR RefSeq; WP_003112823.1; NZ_QZGE01000004.1.
DR PDB; 5DIR; X-ray; 2.80 A; A/B/C/D=1-169.
DR PDB; 6FMS; X-ray; 3.00 A; A/B/C/D=2-169.
DR PDBsum; 5DIR; -.
DR PDBsum; 6FMS; -.
DR AlphaFoldDB; Q9HVM5; -.
DR SMR; Q9HVM5; -.
DR STRING; 287.DR97_1863; -.
DR PaxDb; Q9HVM5; -.
DR DNASU; 877620; -.
DR EnsemblBacteria; AAG07947; AAG07947; PA4559.
DR GeneID; 877620; -.
DR KEGG; pae:PA4559; -.
DR PATRIC; fig|208964.12.peg.4771; -.
DR PseudoCAP; PA4559; -.
DR HOGENOM; CLU_083252_4_0_6; -.
DR InParanoid; Q9HVM5; -.
DR OMA; NRWYFPA; -.
DR PhylomeDB; Q9HVM5; -.
DR BioCyc; PAER208964:G1FZ6-4652-MON; -.
DR UniPathway; UPA00665; -.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:PseudoCAP.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; ISS:PseudoCAP.
DR GO; GO:0006465; P:signal peptide processing; ISS:PseudoCAP.
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 inner membrane; Cell membrane;
KW Hydrolase; Membrane; Protease; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..169
FT /note="Lipoprotein signal peptidase"
FT /id="PRO_0000178802"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:26912896,
FT ECO:0000269|PubMed:30272004, ECO:0007744|PDB:5DIR,
FT ECO:0007744|PDB:6FMS"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00161,
FT ECO:0000269|PubMed:26912896, ECO:0000269|PubMed:30272004,
FT ECO:0007744|PDB:5DIR, ECO:0007744|PDB:6FMS"
FT TOPO_DOM 31..67
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:26912896,
FT ECO:0000269|PubMed:30272004, ECO:0007744|PDB:5DIR,
FT ECO:0007744|PDB:6FMS"
FT TRANSMEM 68..89
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:26912896,
FT ECO:0000269|PubMed:30272004, ECO:0007744|PDB:5DIR,
FT ECO:0007744|PDB:6FMS"
FT TOPO_DOM 90..96
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:26912896,
FT ECO:0000269|PubMed:30272004, ECO:0007744|PDB:5DIR,
FT ECO:0007744|PDB:6FMS"
FT TRANSMEM 97..118
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:26912896,
FT ECO:0000269|PubMed:30272004, ECO:0007744|PDB:5DIR,
FT ECO:0007744|PDB:6FMS"
FT TOPO_DOM 119..140
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:26912896,
FT ECO:0000269|PubMed:30272004, ECO:0007744|PDB:5DIR,
FT ECO:0007744|PDB:6FMS"
FT TRANSMEM 141..154
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:26912896,
FT ECO:0007744|PDB:5DIR"
FT TOPO_DOM 155..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:26912896,
FT ECO:0007744|PDB:5DIR"
FT ACT_SITE 124
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00161,
FT ECO:0000305|PubMed:26912896"
FT ACT_SITE 143
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00161,
FT ECO:0000305|PubMed:26912896"
FT MUTAGEN 115
FT /note="D->A: Retains 20% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:26912896"
FT MUTAGEN 115
FT /note="D->N: Retains 50% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:26912896"
FT MUTAGEN 116
FT /note="R->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:26912896"
FT MUTAGEN 124
FT /note="D->N: Loss of activity."
FT /evidence="ECO:0000269|PubMed:26912896"
FT MUTAGEN 143
FT /note="D->N: Loss of activity."
FT /evidence="ECO:0000269|PubMed:26912896"
FT TURN 4..6
FT /evidence="ECO:0007829|PDB:5DIR"
FT HELIX 10..12
FT /evidence="ECO:0007829|PDB:5DIR"
FT HELIX 13..33
FT /evidence="ECO:0007829|PDB:5DIR"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:5DIR"
FT TURN 44..46
FT /evidence="ECO:0007829|PDB:5DIR"
FT STRAND 47..54
FT /evidence="ECO:0007829|PDB:5DIR"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:5DIR"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:6FMS"
FT HELIX 69..89
FT /evidence="ECO:0007829|PDB:5DIR"
FT HELIX 96..118
FT /evidence="ECO:0007829|PDB:5DIR"
FT STRAND 119..130
FT /evidence="ECO:0007829|PDB:5DIR"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:5DIR"
FT HELIX 141..154
FT /evidence="ECO:0007829|PDB:5DIR"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:5DIR"
SQ SEQUENCE 169 AA; 18997 MW; 1AE91A4B6B60006F CRC64;
MPDVDRFGRL PWLWITVLVF VLDQVSKAFF QAELSMYQQI VVIPDLFSWT LAYNTGAAFS
FLADSSGWQR WLFALIAIVV SASLVVWLKR LKKGETWLAI ALALVLGGAL GNLYDRMVLG
HVVDFILVHW QNRWYFPAFN LADSAITVGA VMLALDMFRS KKSGEAAHG
