LASA_PSEAE
ID LASA_PSEAE Reviewed; 418 AA.
AC P14789; P72165; Q9I2M5;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 3.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Protease LasA;
DE EC=3.4.24.-;
DE AltName: Full=Staphylolytic protease;
DE Flags: Precursor;
GN Name=lasA; OrderedLocusNames=PA1871;
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 [GENOMIC DNA].
RC STRAIN=PAO;
RX PubMed=2836371; DOI=10.1128/jb.170.6.2784-2789.1988;
RA Schad P.A., Iglewski B.H.;
RT "Nucleotide sequence and expression in Escherichia coli of the Pseudomonas
RT aeruginosa lasA gene.";
RL J. Bacteriol. 170:2784-2789(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SEQUENCE REVISION.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=2123032; DOI=10.1093/nar/18.21.6444;
RA Darzins A., Peters J.E., Galloway D.R.;
RT "Revised nucleotide sequence of the lasA gene from Pseudomonas aeruginosa
RT PAO1.";
RL Nucleic Acids Res. 18:6444-6444(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP PROTEOLYTIC CLEAVAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF HIS-356.
RC STRAIN=FRD1;
RX PubMed=8932318; DOI=10.1128/jb.178.22.6608-6617.1996;
RA Gustin J.K., Kessler E., Ohman D.E.;
RT "A substitution at His-120 in the LasA protease of Pseudomonas aeruginosa
RT blocks enzymatic activity without affecting propeptide processing or
RT extracellular secretion.";
RL J. Bacteriol. 178:6608-6617(1996).
RN [4]
RP PROTEIN SEQUENCE OF 32-41, SUBCELLULAR LOCATION, AND PROTEOLYTIC CLEAVAGE.
RC STRAIN=PAO1 / PAO25;
RX PubMed=9642203; DOI=10.1128/jb.180.13.3467-3469.1998;
RA Braun P., de Groot A., Bitter W., Tommassen J.;
RT "Secretion of elastinolytic enzymes and their propeptides by Pseudomonas
RT aeruginosa.";
RL J. Bacteriol. 180:3467-3469(1998).
RN [5]
RP PROTEIN SEQUENCE OF 237-243, FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1, and PA220;
RX PubMed=2110137; DOI=10.1128/jb.172.5.2236-2240.1990;
RA Peters J.E., Galloway D.R.;
RT "Purification and characterization of an active fragment of the LasA
RT protein from Pseudomonas aeruginosa: enhancement of elastase activity.";
RL J. Bacteriol. 172:2236-2240(1990).
RN [6]
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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1, DG1, and FRD1 / FRD2;
RX PubMed=1597429; DOI=10.1128/jb.174.12.4140-4147.1992;
RA Olson J.C., Ohman D.E.;
RT "Efficient production and processing of elastase and LasA by Pseudomonas
RT aeruginosa require zinc and calcium ions.";
RL J. Bacteriol. 174:4140-4147(1992).
RN [8]
RP FUNCTION, SUBSTRATE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC STRAIN=PA220;
RX PubMed=11179971; DOI=10.1046/j.1432-1327.2001.01967.x;
RA Vessillier S., Delolme F., Bernillon J., Saulnier J., Wallach J.;
RT "Hydrolysis of glycine-containing elastin pentapeptides by LasA, a
RT metalloelastase from Pseudomonas aeruginosa.";
RL Eur. J. Biochem. 268:1049-1057(2001).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 237-418 IN COMPLEX WITH ZINC WITH
RP OR WITHOUT PRODUCT ANALOG, PROTEIN SEQUENCE OF 237-246, BIOPHYSICOCHEMICAL
RP PROPERTIES, REACTION MECHANISM, MASS SPECTROMETRY, ACTIVE SITE, AND
RP DISULFIDE BOND.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=20026068; DOI=10.1016/j.jmb.2009.12.021;
RA Spencer J., Murphy L.M., Conners R., Sessions R.B., Gamblin S.J.;
RT "Crystal structure of the LasA virulence factor from Pseudomonas
RT aeruginosa: substrate specificity and mechanism of M23 metallopeptidases.";
RL J. Mol. Biol. 396:908-923(2010).
CC -!- FUNCTION: Involved in proteolysis and elastolysis (degradation of the
CC host protein elastin). Has staphylolytic activity (degrades
CC pentaglycine cross-links in cell wall peptidogylcan), preferring Gly-
CC Gly-|-X substrates where X is Ala or Gly (PubMed:11179971). Enhances
CC the elastolytic but not proteolytic activity of elastase (lasB) and
CC elastolytic activity of other proteases (PubMed:2110137). Degradation
CC of host elastin is likely to contribute to the pathogenicity of
CC P.aeruginosa. While either His-317 or His-356 can abstract a proton in
CC the hydrolysis reaction, the same residue performs both functions in a
CC given catalytic cycle, with the other stabilizing the catalytic
CC intermediate (PubMed:20026068). {ECO:0000269|PubMed:11179971,
CC ECO:0000269|PubMed:1597429, ECO:0000269|PubMed:20026068,
CC ECO:0000269|PubMed:2110137, ECO:0000269|PubMed:8932318}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:20026068};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:20026068};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=58 uM for Dabsyl-Leu-Gly-Gly-Gly-Ala-Edans at pH 9
CC {ECO:0000269|PubMed:20026068};
CC KM=61 uM for Dabsyl-Leu-Gly-Gly-Gly-Ala-Edans at pH 8
CC {ECO:0000269|PubMed:20026068};
CC KM=105 uM for Dabsyl-Leu-Gly-Gly-Gly-Ala-Edans at pH 7
CC {ECO:0000269|PubMed:20026068};
CC Note=kcat is 5.1 sec(-1), 5.3 sec(-1), 1.7 sec(-1) at pH 9, 8 and 7
CC respectively. {ECO:0000269|PubMed:20026068};
CC pH dependence:
CC Optimum pH is 8-9, inactive at pH 6 and below.
CC {ECO:0000269|PubMed:20026068};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11179971,
CC ECO:0000269|PubMed:1597429, ECO:0000269|PubMed:2110137,
CC ECO:0000269|PubMed:9642203}. Note=Secreted in an Xcp-dependent fashion
CC (a type II secretion pathway). {ECO:0000269|PubMed:9642203}.
CC -!- INDUCTION: Optimal protein expression in vivo requires both Zn(2+) and
CC Ca(2+) during growth (at protein level). {ECO:0000269|PubMed:1597429}.
CC -!- PTM: Processing of pro-LasA can occur extracellularly and requires
CC elastase (lasB) (PubMed:9642203). Secretion and processing may be
CC linked (PubMed:8932318). {ECO:0000269|PubMed:8932318,
CC ECO:0000269|PubMed:9642203}.
CC -!- MASS SPECTROMETRY: Mass=19963; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:20026068};
CC -!- DISRUPTION PHENOTYPE: Loss of staphylolytic activity (lysis of heat-
CC killed S.aureus). {ECO:0000269|PubMed:8932318}.
CC -!- SIMILARITY: Belongs to the peptidase M23A family. {ECO:0000305}.
CC -!- CAUTION: Partial protein sequence was obtained following expression in
CC E.coli, not P.aeruginosa. {ECO:0000305|PubMed:8932318}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA25873.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA25873.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA39397.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M20982; AAA25873.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X55904; CAA39397.1; ALT_INIT; Genomic_DNA.
DR EMBL; U68175; AAC12656.1; -; Genomic_DNA.
DR EMBL; AE004091; AAG05260.1; -; Genomic_DNA.
DR PIR; A46076; A46076.
DR PIR; F83411; F83411.
DR RefSeq; NP_250562.1; NC_002516.2.
DR RefSeq; WP_010895585.1; NZ_QZGE01000003.1.
DR PDB; 3IT5; X-ray; 2.00 A; A/B/E/G=237-418.
DR PDB; 3IT7; X-ray; 2.14 A; A/B=237-418.
DR PDBsum; 3IT5; -.
DR PDBsum; 3IT7; -.
DR AlphaFoldDB; P14789; -.
DR SMR; P14789; -.
DR STRING; 287.DR97_4; -.
DR MEROPS; M23.002; -.
DR PaxDb; P14789; -.
DR PRIDE; P14789; -.
DR EnsemblBacteria; AAG05260; AAG05260; PA1871.
DR GeneID; 878260; -.
DR KEGG; pae:PA1871; -.
DR PATRIC; fig|208964.12.peg.1948; -.
DR PseudoCAP; PA1871; -.
DR HOGENOM; CLU_656977_0_0_6; -.
DR InParanoid; P14789; -.
DR OMA; ATNYYHM; -.
DR BioCyc; PAER208964:G1FZ6-1911-MON; -.
DR BRENDA; 3.4.24.B16; 5087.
DR EvolutionaryTrace; P14789; -.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0005615; C:extracellular space; IDA:PseudoCAP.
DR GO; GO:0004175; F:endopeptidase activity; IDA:CACAO.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0009253; P:peptidoglycan catabolic process; IDA:CACAO.
DR GO; GO:0015628; P:protein secretion by the type II secretion system; IDA:PseudoCAP.
DR GO; GO:0043952; P:protein transport by the Sec complex; IDA:PseudoCAP.
DR GO; GO:0006508; P:proteolysis; IDA:PseudoCAP.
DR GO; GO:0000920; P:septum digestion after cytokinesis; IBA:GO_Central.
DR Gene3D; 2.70.70.10; -; 1.
DR InterPro; IPR011055; Dup_hybrid_motif.
DR InterPro; IPR000841; Pept_M23A_Blytic.
DR InterPro; IPR016047; Peptidase_M23.
DR Pfam; PF01551; Peptidase_M23; 1.
DR PRINTS; PR00933; BLYTICPTASE.
DR SUPFAM; SSF51261; SSF51261; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Secreted;
KW Signal; Virulence; Zinc; Zymogen.
FT SIGNAL 1..31
FT /evidence="ECO:0000303|PubMed:8932318"
FT PROPEP 32..236
FT /evidence="ECO:0000269|PubMed:2110137,
FT ECO:0000269|PubMed:9642203"
FT /id="PRO_0000026812"
FT CHAIN 237..418
FT /note="Protease LasA"
FT /id="PRO_0000026813"
FT ACT_SITE 317
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:20026068"
FT ACT_SITE 356
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:20026068"
FT BINDING 259
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:20026068"
FT BINDING 272
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:20026068"
FT BINDING 358
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:20026068"
FT DISULFID 301..347
FT /evidence="ECO:0007744|PDB:3IT5, ECO:0007744|PDB:3IT7"
FT DISULFID 391..406
FT /evidence="ECO:0007744|PDB:3IT5, ECO:0007744|PDB:3IT7"
FT MUTAGEN 356
FT /note="H->A: Loss of staphylolytic activity; mature protein
FT is still produced."
FT /evidence="ECO:0000269|PubMed:8932318"
FT CONFLICT 80
FT /note="L -> V (in Ref. 3; AAC12656)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="P -> R (in Ref. 1; AAA25873)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="V -> A (in Ref. 3; AAC12656)"
FT /evidence="ECO:0000305"
FT CONFLICT 196..202
FT /note="QGGNPLG -> ARRQSAR (in Ref. 1; AAA25873)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="S -> R (in Ref. 3; AAC12656)"
FT /evidence="ECO:0000305"
FT CONFLICT 260..262
FT /note="SNT -> FEH (in Ref. 1; AAA25873)"
FT /evidence="ECO:0000305"
FT TURN 240..242
FT /evidence="ECO:0007829|PDB:3IT5"
FT STRAND 252..255
FT /evidence="ECO:0007829|PDB:3IT5"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:3IT5"
FT STRAND 270..276
FT /evidence="ECO:0007829|PDB:3IT5"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:3IT5"
FT STRAND 290..299
FT /evidence="ECO:0007829|PDB:3IT5"
FT STRAND 302..306
FT /evidence="ECO:0007829|PDB:3IT5"
FT STRAND 310..320
FT /evidence="ECO:0007829|PDB:3IT5"
FT STRAND 334..338
FT /evidence="ECO:0007829|PDB:3IT5"
FT HELIX 342..345
FT /evidence="ECO:0007829|PDB:3IT5"
FT TURN 346..348
FT /evidence="ECO:0007829|PDB:3IT5"
FT STRAND 353..355
FT /evidence="ECO:0007829|PDB:3IT5"
FT STRAND 357..363
FT /evidence="ECO:0007829|PDB:3IT5"
FT STRAND 378..381
FT /evidence="ECO:0007829|PDB:3IT5"
FT TURN 391..393
FT /evidence="ECO:0007829|PDB:3IT5"
FT STRAND 394..398
FT /evidence="ECO:0007829|PDB:3IT5"
FT TURN 399..401
FT /evidence="ECO:0007829|PDB:3IT5"
SQ SEQUENCE 418 AA; 45517 MW; 48E293A1EA624DC0 CRC64;
MQHKRSRAMA SPRSPFLFVL LALAVGGTAN AHDDGLPAFR YSAELLGQLQ LPSVALPLND
DLFLYGRDAE AFDLEAYLAL NAPALRDKSE YLEHWSGYYS INPKVLLTLM VMQSGPLGAP
DERALAAPLG RLSAKRGFDA QVRDVLQQLS RRYYGFEEYQ LRQAAARKAV GEDGLNAASA
ALLGLLREGA KVSAVQGGNP LGAYAQTFQR LFGTPAAELL QPSNRVARQL QAKAALAPPS
NLMQLPWRQG YSWQPNGAHS NTGSGYPYSS FDASYDWPRW GSATYSVVAA HAGTVRVLSR
CQVRVTHPSG WATNYYHMDQ IQVSNGQQVS ADTKLGVYAG NINTALCEGG SSTGPHLHFS
LLYNGAFVSL QGASFGPYRI NVGTSNYDND CRRYYFYNQS AGTTHCAFRP LYNPGLAL
