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Protein

Protease LasA

Gene

lasA

Organism
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in proteolysis and elastolysis (degradation of the host protein elastin). Has staphylolytic activity (degrades pentaglycine cross-links in cell wall peptidogylcan), preferring Gly-Gly-|-X substrates where X is Ala or Gly (PubMed:11179971). Enhances the elastolytic but not proteolytic activity of elastase (lasB) and elastolytic activity of other proteases (PubMed:2110137). Degradation of host elastin is likely to contribute to the pathogenicity of P.aeruginosa. While either His-317 or His-356 can abstract a proton in the hydrolysis reaction, the same residue performs both functions in a given catalytic cycle, with the other stabilizing the catalytic intermediate (PubMed:20026068).5 Publications

Cofactori

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Kineticsi

kcat is 5.1 s(-1), 5.3 s(-1), 1.7 s(-1) at pH 9, 8 and 7 respectively.1 Publication

  1. KM=58 µM for Dabsyl-Leu-Gly-Gly-Gly-Ala-Edans at pH 91 Publication
  2. KM=61 µM for Dabsyl-Leu-Gly-Gly-Gly-Ala-Edans at pH 81 Publication
  3. KM=105 µM for Dabsyl-Leu-Gly-Gly-Gly-Ala-Edans at pH 71 Publication

    pH dependencei

    Optimum pH is 8-9, inactive at pH 6 and below.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi259 – 2591Zinc; via tele nitrogen1 Publication
    Metal bindingi272 – 2721Zinc1 Publication
    Active sitei317 – 3171Proton donor/acceptor1 Publication
    Active sitei356 – 3561Proton donor/acceptor1 Publication
    Metal bindingi358 – 3581Zinc; via pros nitrogen1 Publication

    GO - Molecular functioni

    • endopeptidase activity Source: PseudoCAP
    • metal ion binding Source: UniProtKB-KW
    • metalloendopeptidase activity Source: InterPro

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Biological processi

    Virulence

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi3.4.24.B16. 5087.

    Protein family/group databases

    MEROPSiM23.002.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protease LasA (EC:3.4.24.-)
    Alternative name(s):
    Staphylolytic protease
    Gene namesi
    Name:lasA
    Ordered Locus Names:PA1871
    OrganismiPseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
    Taxonomic identifieri208964 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaPseudomonadalesPseudomonadaceaePseudomonas
    Proteomesi
    • UP000002438 Componenti: Chromosome

    Organism-specific databases

    PseudoCAPiPA1871.

    Subcellular locationi

    • Secreted 4 Publications

    • Note: Secreted in an Xcp-dependent fashion (a type II secretion pathway).1 Publication

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Disruption phenotypei

    Loss of staphylolytic activity (lysis of heat-killed S.aureus).1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi356 – 3561H → A: Loss of staphylolytic activity; mature protein is still produced. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 31311 PublicationAdd
    BLAST
    Propeptidei32 – 2362052 PublicationsPRO_0000026812Add
    BLAST
    Chaini237 – 418182Protease LasAPRO_0000026813Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi301 ↔ 347Combined sources
    Disulfide bondi391 ↔ 406Combined sources

    Post-translational modificationi

    Processing of pro-LasA can occur extracellularly and requires elastase (lasB) (PubMed:9642203). Secretion and processing may be linked (PubMed:8932318).2 Publications

    Keywords - PTMi

    Disulfide bond, Zymogen

    Proteomic databases

    PaxDbiP14789.

    Expressioni

    Inductioni

    Optimal protein expression in vivo requires both Zn2+ and Ca2+ during growth (at protein level).1 Publication

    Interactioni

    Protein-protein interaction databases

    STRINGi208964.PA1871.

    Structurei

    Secondary structure

    1
    418
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni240 – 2423Combined sources
    Beta strandi252 – 2554Combined sources
    Beta strandi263 – 2675Combined sources
    Beta strandi270 – 2767Combined sources
    Beta strandi286 – 2883Combined sources
    Beta strandi290 – 29910Combined sources
    Beta strandi302 – 3065Combined sources
    Beta strandi310 – 32011Combined sources
    Beta strandi334 – 3385Combined sources
    Helixi342 – 3454Combined sources
    Turni346 – 3483Combined sources
    Beta strandi353 – 3553Combined sources
    Beta strandi357 – 3637Combined sources
    Beta strandi378 – 3814Combined sources
    Turni391 – 3933Combined sources
    Beta strandi394 – 3985Combined sources
    Turni399 – 4013Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3IT5X-ray2.00A/B/E/G237-418[»]
    3IT7X-ray2.14A/B237-418[»]
    ProteinModelPortaliP14789.
    SMRiP14789. Positions 237-418.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP14789.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase M23A family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiENOG4108VC8. Bacteria.
    COG0739. LUCA.
    HOGENOMiHOG000274301.
    InParanoidiP14789.
    KOiK08642.
    OMAiATNYYHM.
    OrthoDBiEOG6XWTXV.

    Family and domain databases

    InterProiIPR011055. Dup_hybrid_motif.
    IPR000841. Pept_M23A_Blytic.
    IPR016047. Peptidase_M23.
    [Graphical view]
    PfamiPF01551. Peptidase_M23. 1 hit.
    [Graphical view]
    PRINTSiPR00933. BLYTICPTASE.
    SUPFAMiSSF51261. SSF51261. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P14789-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MQHKRSRAMA SPRSPFLFVL LALAVGGTAN AHDDGLPAFR YSAELLGQLQ
    60 70 80 90 100
    LPSVALPLND DLFLYGRDAE AFDLEAYLAL NAPALRDKSE YLEHWSGYYS
    110 120 130 140 150
    INPKVLLTLM VMQSGPLGAP DERALAAPLG RLSAKRGFDA QVRDVLQQLS
    160 170 180 190 200
    RRYYGFEEYQ LRQAAARKAV GEDGLNAASA ALLGLLREGA KVSAVQGGNP
    210 220 230 240 250
    LGAYAQTFQR LFGTPAAELL QPSNRVARQL QAKAALAPPS NLMQLPWRQG
    260 270 280 290 300
    YSWQPNGAHS NTGSGYPYSS FDASYDWPRW GSATYSVVAA HAGTVRVLSR
    310 320 330 340 350
    CQVRVTHPSG WATNYYHMDQ IQVSNGQQVS ADTKLGVYAG NINTALCEGG
    360 370 380 390 400
    SSTGPHLHFS LLYNGAFVSL QGASFGPYRI NVGTSNYDND CRRYYFYNQS
    410
    AGTTHCAFRP LYNPGLAL
    Length:418
    Mass (Da):45,517
    Last modified:January 11, 2001 - v3
    Checksum:i48E293A1EA624DC0
    GO

    Sequence cautioni

    The sequence AAA25873.1 differs from that shown. Reason: Frameshift at position 378. Curated
    The sequence AAA25873.1 differs from that shown. Reason: Erroneous termination at position 395. Translated as Tyr.Curated
    The sequence CAA39397.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti80 – 801L → V in AAC12656 (PubMed:8932318).Curated
    Sequence conflicti128 – 1281P → R in AAA25873 (PubMed:2836371).Curated
    Sequence conflicti192 – 1921V → A in AAC12656 (PubMed:8932318).Curated
    Sequence conflicti196 – 2027QGGNPLG → ARRQSAR in AAA25873 (PubMed:2836371).Curated
    Sequence conflicti223 – 2231S → R in AAC12656 (PubMed:8932318).Curated
    Sequence conflicti260 – 2623SNT → FEH in AAA25873 (PubMed:2836371).Curated

    Mass spectrometryi

    Molecular mass is 19963 Da from positions 237 - 418. Determined by ESI. 1 Publication

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M20982 Genomic DNA. Translation: AAA25873.1. Sequence problems.
    X55904 Genomic DNA. Translation: CAA39397.1. Different initiation.
    U68175 Genomic DNA. Translation: AAC12656.1.
    AE004091 Genomic DNA. Translation: AAG05260.1.
    PIRiA46076.
    F83411.
    RefSeqiNP_250562.1. NC_002516.2.
    WP_010895585.1. NZ_ASJY01000253.1.

    Genome annotation databases

    EnsemblBacteriaiAAG05260; AAG05260; PA1871.
    GeneIDi878260.
    KEGGipae:PA1871.
    PATRICi19838135. VBIPseAer58763_1948.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M20982 Genomic DNA. Translation: AAA25873.1. Sequence problems.
    X55904 Genomic DNA. Translation: CAA39397.1. Different initiation.
    U68175 Genomic DNA. Translation: AAC12656.1.
    AE004091 Genomic DNA. Translation: AAG05260.1.
    PIRiA46076.
    F83411.
    RefSeqiNP_250562.1. NC_002516.2.
    WP_010895585.1. NZ_ASJY01000253.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3IT5X-ray2.00A/B/E/G237-418[»]
    3IT7X-ray2.14A/B237-418[»]
    ProteinModelPortaliP14789.
    SMRiP14789. Positions 237-418.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi208964.PA1871.

    Protein family/group databases

    MEROPSiM23.002.

    Proteomic databases

    PaxDbiP14789.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAG05260; AAG05260; PA1871.
    GeneIDi878260.
    KEGGipae:PA1871.
    PATRICi19838135. VBIPseAer58763_1948.

    Organism-specific databases

    PseudoCAPiPA1871.

    Phylogenomic databases

    eggNOGiENOG4108VC8. Bacteria.
    COG0739. LUCA.
    HOGENOMiHOG000274301.
    InParanoidiP14789.
    KOiK08642.
    OMAiATNYYHM.
    OrthoDBiEOG6XWTXV.

    Enzyme and pathway databases

    BRENDAi3.4.24.B16. 5087.

    Miscellaneous databases

    EvolutionaryTraceiP14789.

    Family and domain databases

    InterProiIPR011055. Dup_hybrid_motif.
    IPR000841. Pept_M23A_Blytic.
    IPR016047. Peptidase_M23.
    [Graphical view]
    PfamiPF01551. Peptidase_M23. 1 hit.
    [Graphical view]
    PRINTSiPR00933. BLYTICPTASE.
    SUPFAMiSSF51261. SSF51261. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Nucleotide sequence and expression in Escherichia coli of the Pseudomonas aeruginosa lasA gene."
      Schad P.A., Iglewski B.H.
      J. Bacteriol. 170:2784-2789(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: PAO.
    2. "Revised nucleotide sequence of the lasA gene from Pseudomonas aeruginosa PAO1."
      Darzins A., Peters J.E., Galloway D.R.
      Nucleic Acids Res. 18:6444-6444(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SEQUENCE REVISION.
      Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228.
    3. "A substitution at His-120 in the LasA protease of Pseudomonas aeruginosa blocks enzymatic activity without affecting propeptide processing or extracellular secretion."
      Gustin J.K., Kessler E., Ohman D.E.
      J. Bacteriol. 178:6608-6617(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, PROTEOLYTIC CLEAVAGE, DISRUPTION PHENOTYPE, MUTAGENESIS OF HIS-356.
      Strain: FRD1.
    4. "Secretion of elastinolytic enzymes and their propeptides by Pseudomonas aeruginosa."
      Braun P., de Groot A., Bitter W., Tommassen J.
      J. Bacteriol. 180:3467-3469(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 32-41, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE.
      Strain: PAO1 / PAO25.
    5. "Purification and characterization of an active fragment of the LasA protein from Pseudomonas aeruginosa: enhancement of elastase activity."
      Peters J.E., Galloway D.R.
      J. Bacteriol. 172:2236-2240(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 237-243, FUNCTION, SUBCELLULAR LOCATION.
      Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228 and PA220.
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228.
    7. "Efficient production and processing of elastase and LasA by Pseudomonas aeruginosa require zinc and calcium ions."
      Olson J.C., Ohman D.E.
      J. Bacteriol. 174:4140-4147(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION.
      Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228, DG1 and FRD1 / FRD2.
    8. "Hydrolysis of glycine-containing elastin pentapeptides by LasA, a metalloelastase from Pseudomonas aeruginosa."
      Vessillier S., Delolme F., Bernillon J., Saulnier J., Wallach J.
      Eur. J. Biochem. 268:1049-1057(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBSTRATE SPECIFICITY, SUBCELLULAR LOCATION.
      Strain: PA220.
    9. "Crystal structure of the LasA virulence factor from Pseudomonas aeruginosa: substrate specificity and mechanism of M23 metallopeptidases."
      Spencer J., Murphy L.M., Conners R., Sessions R.B., Gamblin S.J.
      J. Mol. Biol. 396:908-923(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 237-418 IN COMPLEX WITH ZINC WITH OR WITHOUT PRODUCT ANALOG, PROTEIN SEQUENCE OF 237-246, BIOPHYSICOCHEMICAL PROPERTIES, REACTION MECHANISM, MASS SPECTROMETRY, ACTIVE SITE, DISULFIDE BOND.
      Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228.

    Entry informationi

    Entry nameiLASA_PSEAE
    AccessioniPrimary (citable) accession number: P14789
    Secondary accession number(s): P72165, Q9I2M5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: January 11, 2001
    Last modified: January 20, 2016
    This is version 112 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Caution

    Partial protein sequence was obtained following expression in E.coli, not P.aeruginosa.1 Publication

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.