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Information on EC 3.4.23.48 - plasminogen activator Pla
for references in articles please use BRENDA:EC3.4.23.48
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EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.23 Aspartic endopeptidases
3.4.23.48 plasminogen activator Pla
IUBMB Comments
In peptidase family A26. From the bacterium Yersinia pestis that causes plague.
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
- 3.4.23.48
- aureus
-
staphylococci
-
methicillin-resistant
-
microbiological
- methicillin
- vancomycin
-
nosocomial
- epidermidis
- gentamicin
- mastitis
-
catheter
- enterotoxin
- oxacillin
-
swab
- ciprofloxacin
-
bacteriological
-
cocci
- amikacin
- clindamycin
-
enterococci
- saprophyticus
- haemolyticus
-
staph
- bacteremia
-
methicillin-susceptible
-
catheter-related
- viridans
- mupirocin
-
tsst-1
-
antibiograms
- linezolid
- xylosus
-
kirby-bauer
-
panton-valentine
- hyicus
- ceftazidime
- thermonuclease
- cefoxitin
- analysis
- medicine
-
leukocidin
- teicoplanin
-
methicillin-sensitive
- endophthalmitis
- warneri
-
fusidic
-
sccmec
-
toxin-1
- imipenem
-
ca-mrsa
-
bactec
- capitis
Reaction Schemes
showConverts human Glu-plasminogen to plasmin by cleaving the Arg560-/-Val peptide bond that is also hydrolysed by the mammalian u-plasminogen activator and t-plasminogen activator. Also cleaves arginyl bonds in other proteins
Synonyms
coagulase, plasminogen activator pla, pla protease, plasminogen activator protease pla, beta-pla, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
coagulase
fibrinolysin
Pla
Pla protease
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Converts human Glu-plasminogen to plasmin by cleaving the Arg560-/-Val peptide bond that is also hydrolysed by the mammalian u-plasminogen activator and t-plasminogen activator. Also cleaves arginyl bonds in other proteins
Converts human Glu-plasminogen to plasmin by cleaving the Arg560-/-Val peptide bond that is also hydrolysed by the mammalian u-plasminogen activator and t-plasminogen activator. Also cleaves arginyl bonds in other proteins
-
-
-
-
Converts human Glu-plasminogen to plasmin by cleaving the Arg560-/-Val peptide bond that is also hydrolysed by the mammalian u-plasminogen activator and t-plasminogen activator. Also cleaves arginyl bonds in other proteins
distribution of residues within the active site cleft strongly suggests that the arginine side chain of the substrate will bind in a deep, negatively charged pocket formed by Pla residues E29, D204, D206, and E217. The two valine residues C-terminal to the scissile bond will likely bind in the shallow, hydrophobic pocket located on the other side of the plane formed by the active site residues D84, H208, and the nucleophilic water molecule
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
101028-08-4
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(DABCYL)-Arg-Arg-Ile-Asn-Arg-Glu-(EDANS)-NH2 + H2O
(DABCYL)-Arg + Arg-Ile-Asn-Arg-Glu-(EDANS)-NH2
C3 protein of complement system + H2O
fragments of C3 protein of complement system
-
Substrates: -
Products: -
Products: -
?
complement C3 + H2O
?
-
Substrates: Pla proteolyzes complement C3 which may amiliorate the host inflammatory response by abolishing its chemoattractant properties
Products: -
Products: -
?
human alpha2-antiplasmin + H2O
fragments of alpha2-antiplasmin
-
Substrates: -
Products: -
Products: -
?
human Glu-plasminogen + H2O
plasmin + ?
-
Substrates: Pla activates Glu-plasminogen to plasmin, in vitro, TFPI is found to be a much better substrate for Pla than plasminogen
Products: -
Products: -
?
human tissue factor pathway inhibitor + H2O
?
-
Substrates: Pla can proteolytically degrade TFPI, completely abrogating its anticoagulant function. In vitro, TFPI is found to be a much better substrate for Pla than plasminogen
Products: -
Products: -
?
YapE + H2O
?
Substrates: Yersinia pestis autotransporter YapE protein
Products: cleavage of YapE occurs in Yersinia pestis but not in the enteric Yersinia species, and requires the omptin Pla
Products: cleavage of YapE occurs in Yersinia pestis but not in the enteric Yersinia species, and requires the omptin Pla
?
YapG + H2O
?
Substrates: Yersinia pestis autotransporter YapG protein
Products: sites K512, (K548-R549) and K594-R595 represent the primary cleavage sites of YapG, whereas sites K'558 and K'604 represent the secondary alternative cleavage sites
Products: sites K512, (K548-R549) and K594-R595 represent the primary cleavage sites of YapG, whereas sites K'558 and K'604 represent the secondary alternative cleavage sites
?
Yersinia outer proteins + H2O
fragments of Yersinia outer proteins
-
Substrates: -
Products: -
Products: -
?
zymogen factor VII + H2O
factor VIIa
-
Substrates: Pla proteolytically converts zymogen factor VII to the active form, factor VIIa. Pla activates factor VII about twice as fast as it activates plasminogen
Products: -
Products: -
?
(DABCYL)-Arg-Arg-Ile-Asn-Arg-Glu-(EDANS)-NH2 + H2O
(DABCYL)-Arg + Arg-Ile-Asn-Arg-Glu-(EDANS)-NH2
Substrates: -
Products: -
Products: -
?
(DABCYL)-Arg-Arg-Ile-Asn-Arg-Glu-(EDANS)-NH2 + H2O
(DABCYL)-Arg + Arg-Ile-Asn-Arg-Glu-(EDANS)-NH2
Substrates: -
Products: -
Products: -
?
(DABCYL)-Arg-Arg-Ile-Asn-Arg-Glu-(EDANS)-NH2 + H2O
(DABCYL)-Arg + Arg-Ile-Asn-Arg-Glu-(EDANS)-NH2
Substrates: -
Products: -
Products: -
?
alpha2-antiplasmin + H2O
?
-
Substrates: Pla inactivates the main physiologic inhibitor of plasmin
Products: -
Products: -
?
alpha2-antiplasmin + H2O
?
-
Substrates: Pla inactivates alpha2-antiplasmin
Products: -
Products: -
?
alpha2-antiplasmin + H2O
?
Substrates: alpha2AP is the main inhibitor of free plasmin in the circulation. Pla cleaves and inactivates alpha2AP by a single, rapid cut. It appears likely that the R376-M377 bait peptide bond is targeted by Pla
Products: -
Products: -
?
D-Val-Leu-Lys-p-nitroanilide + H2O
D-Val-Leu-Lys + p-nitroaniline
-
Substrates: Lpa gene encoding a homologue of the plasminogen activator Pla of Yersinia pestis identified, described as a surface protease exhibiting plasminogen activator activity, plasminogen activity of inner and outer membranes measured
Products: -
Products: -
?
D-Val-Leu-Lys-p-nitroanilide + H2O
D-Val-Leu-Lys + p-nitroaniline
-
Substrates: Lpa gene encoding a homologue of the plasminogen activator Pla of Yersinia pestis identified, described as a surface protease exhibiting plasminogen activator activity, plasminogen activity of inner and outer membranes measured
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: capacity to convert plasminogen into plasmin by the action of the outer-membrane Lpa protein determined
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: capacity to convert plasminogen into plasmin by the action of the outer-membrane Lpa protein determined
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: activates plasminogen by cleaving the Arg560-Val561 bond
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: Pla also expresses a weak coagulase activity
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: activates plasminogen by cleaving the Arg560-Val561 bond
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: Pla has the additional ability to bind to the basement membrane component type IV collagen rendering adhesive properties to Yersina pestis cells
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: Pla belongs to the omptin family of enterobacterial surface proteases and is responsible for the highly efficient invasion of the plague bacterium from the subcutaneous infection site into the circulation
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: plasminogen activator is a surface virulence factor that contributes to the highly imvasive nature of the pathogen by binding various tissue matrix components
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: cleavage of Arg560-/-Val561
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
Substrates: plasminogen activator Pla shown to be essential to cause primary pneumonic plague, minor importance determined for dissemination during pneumonic plague than during bubonic plague, inhibition of plasminogen activator Pla expression shown to prolong survival of infected mice
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
Substrates: identification and analysis of small-peptide substrates and inhibitors of plasminogen activator Pla by use of parallel synthesis and positional scanning
Products: -
Products: -
?
plasminogen activator inhibitor-1 + H2O
?
-
Substrates: PAI-1 is cleaved and inactivated by the Pla protease of Yersinia pestis in the lung airspace of C57BL/6 mice
Products: -
Products: -
?
plasminogen activator inhibitor-1 + H2O
?
Substrates: inactivation. PAI-1 is the primary physiological inhibitor of uPA and t-PA and a major inhibitor of fibrinolysis. Pla rapidly inactivates PAI-1 by a single cleavage of the bait peptide at R346-M347. In circulation, most PAI-1 is bound to vitronectin, which is also degraded by Pla
Products: -
Products: -
?
plasminogen activator inhibitor-1 + H2O
?
Substrates: inactivation
Products: -
Products: -
?
plasminogen activator inhibitor-1 + H2O
?
-
Substrates: PAI-1 is cleaved and inactivated by the Pla protease of Yersinia pestis in the lung airspace of C57BL/6 mice
Products: -
Products: -
?
TAFI + H2O
TAFIa + ?
Substrates: TAFI is secreted into plasma as a procarboxypeptidase, it is a regulatory protein linking the coagulation and fibrinolytic systems, and TAFI is protective in septic yersionosis. Pla cleaves at the C-terminal region of TAFI and reduces its activation to TAFIa
Products: -
Products: -
?
tissue factor pathway inhibitor + H2O
?
Substrates: TFPI is a major anticoagulant and forms stable TFPI-FXa complexes that block blood clotting. Enzyme Pla cleaves the tissue factor pathway inhibitor, TFPI
Products: -
Products: -
?
tissue factor pathway inhibitor + H2O
?
Substrates: inactivation
Products: -
Products: -
?
additional information
?
-
-
Substrates: plasminogen activator plays a pivotal role in internalisation of bacteria by HeLa cells. Intracellular signalling and cytoskeletal rearrangement is involved in Yersinia pestis plasminogen activator mediated HeLa cell invasion
Products: -
Products: -
?
additional information
?
-
-
Substrates: plasminogen activator Pla is essential for the spread of Yersinia pestis from the subcutaneous infection site into circulation, and the proteolytic activation of plasminogen is involved in virulence function. In addition to proteolysis plasminogen activator Pla promotes bacterial adhesion to mammalian extracellular matrices and epithelial cells as well as bacterial invasion into eukayotic cells. Laminin functions as an adhesion target for plasminogen activator Pla, which also expresses a lower adhesion affinity for heparan sulfate proteoglycan. the adhesion targets are not directly degraded by plasminogen activator Pla, but Pla-mediated generation of plasmin leads to their degradation
Products: -
Products: -
?
additional information
?
-
-
Substrates: no degradation of Val-Leu-Lys-p-nitroanilide. Plasminogen activator degrades outer membrane proteins of Yersinia cell surface and exhibits a weak coagulase activity. In addition to proteolysis plasminogen activator Pla promotes bacterial adhesion to mammalian extracellular matrices and epithelial cells as well as bacterial invasion into eukaryotic cells. Laminin functions as an adhesion target for plasminogen activator Pla, which also expresses a lower adhesion affinity for heparan sulfate proteoglycan. The adhesion targets are not directly degraded by plasminogen activator Pla, but Pla-mediated generation of plasmin leads to their degradation
Products: -
Products: -
?
additional information
?
-
-
Substrates: the invasion of alveolar macrophages by Yersinia pestis depends both in vitro and in vivo on the expression of plasminogen activator Pla. Macrophages and transfectants expressing C-type lectin receptor DEC-205, but not their negative counterparts, phagocytose plasminogen activator Pla-expressing Yersinia pestis and Escherichia coli K12 more efficiently than Pla-negative controls. The interactions between Pla-expressing bacteria and DEC-205-expressing transfectants or alveolar macrophages can be inhibited by an anti-DEC-205 antibody. The blockage of the Pla-DEC-205 interaction reduces the dissemination of Yersinia pestis in mice
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme performs autoproteolysis
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme performs autoproteolysis
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme performs autoproteolysis
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
C3 protein of complement system + H2O
fragments of C3 protein of complement system
-
Substrates: -
Products: -
Products: -
?
human alpha2-antiplasmin + H2O
fragments of alpha2-antiplasmin
-
Substrates: -
Products: -
Products: -
?
TAFI + H2O
TAFIa + ?
Substrates: TAFI is secreted into plasma as a procarboxypeptidase, it is a regulatory protein linking the coagulation and fibrinolytic systems, and TAFI is protective in septic yersionosis. Pla cleaves at the C-terminal region of TAFI and reduces its activation to TAFIa
Products: -
Products: -
?
tissue factor pathway inhibitor + H2O
?
Substrates: TFPI is a major anticoagulant and forms stable TFPI-FXa complexes that block blood clotting. Enzyme Pla cleaves the tissue factor pathway inhibitor, TFPI
Products: -
Products: -
?
YapE + H2O
?
Substrates: Yersinia pestis autotransporter YapE protein
Products: cleavage of YapE occurs in Yersinia pestis but not in the enteric Yersinia species, and requires the omptin Pla
Products: cleavage of YapE occurs in Yersinia pestis but not in the enteric Yersinia species, and requires the omptin Pla
?
YapG + H2O
?
Substrates: Yersinia pestis autotransporter YapG protein
Products: sites K512, (K548-R549) and K594-R595 represent the primary cleavage sites of YapG, whereas sites K'558 and K'604 represent the secondary alternative cleavage sites
Products: sites K512, (K548-R549) and K594-R595 represent the primary cleavage sites of YapG, whereas sites K'558 and K'604 represent the secondary alternative cleavage sites
?
Yersinia outer proteins + H2O
fragments of Yersinia outer proteins
-
Substrates: -
Products: -
Products: -
?
alpha2-antiplasmin + H2O
?
-
Substrates: Pla inactivates alpha2-antiplasmin
Products: -
Products: -
?
alpha2-antiplasmin + H2O
?
Substrates: alpha2AP is the main inhibitor of free plasmin in the circulation. Pla cleaves and inactivates alpha2AP by a single, rapid cut. It appears likely that the R376-M377 bait peptide bond is targeted by Pla
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: capacity to convert plasminogen into plasmin by the action of the outer-membrane Lpa protein determined
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: capacity to convert plasminogen into plasmin by the action of the outer-membrane Lpa protein determined
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: activates plasminogen by cleaving the Arg560-Val561 bond
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: Pla belongs to the omptin family of enterobacterial surface proteases and is responsible for the highly efficient invasion of the plague bacterium from the subcutaneous infection site into the circulation
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: activates plasminogen by cleaving the Arg560-Val561 bond
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: Pla also expresses a weak coagulase activity
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: Pla has the additional ability to bind to the basement membrane component type IV collagen rendering adhesive properties to Yersina pestis cells
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: plasminogen activator is a surface virulence factor that contributes to the highly imvasive nature of the pathogen by binding various tissue matrix components
Products: -
Products: -
?
plasminogen + H2O
plasmin + ?
-
Substrates: -
Products: -
Products: -
?
plasminogen activator inhibitor-1 + H2O
?
-
Substrates: PAI-1 is cleaved and inactivated by the Pla protease of Yersinia pestis in the lung airspace of C57BL/6 mice
Products: -
Products: -
?
plasminogen activator inhibitor-1 + H2O
?
Substrates: inactivation. PAI-1 is the primary physiological inhibitor of uPA and t-PA and a major inhibitor of fibrinolysis. Pla rapidly inactivates PAI-1 by a single cleavage of the bait peptide at R346-M347. In circulation, most PAI-1 is bound to vitronectin, which is also degraded by Pla
Products: -
Products: -
?
plasminogen activator inhibitor-1 + H2O
?
-
Substrates: PAI-1 is cleaved and inactivated by the Pla protease of Yersinia pestis in the lung airspace of C57BL/6 mice
Products: -
Products: -
?
additional information
?
-
-
Substrates: plasminogen activator plays a pivotal role in internalisation of bacteria by HeLa cells. Intracellular signalling and cytoskeletal rearrangement is involved in Yersinia pestis plasminogen activator mediated HeLa cell invasion
Products: -
Products: -
?
additional information
?
-
-
Substrates: plasminogen activator Pla is essential for the spread of Yersinia pestis from the subcutaneous infection site into circulation, and the proteolytic activation of plasminogen is involved in virulence function. In addition to proteolysis plasminogen activator Pla promotes bacterial adhesion to mammalian extracellular matrices and epithelial cells as well as bacterial invasion into eukayotic cells. Laminin functions as an adhesion target for plasminogen activator Pla, which also expresses a lower adhesion affinity for heparan sulfate proteoglycan. the adhesion targets are not directly degraded by plasminogen activator Pla, but Pla-mediated generation of plasmin leads to their degradation
Products: -
Products: -
?
additional information
?
-
-
Substrates: the invasion of alveolar macrophages by Yersinia pestis depends both in vitro and in vivo on the expression of plasminogen activator Pla. Macrophages and transfectants expressing C-type lectin receptor DEC-205, but not their negative counterparts, phagocytose plasminogen activator Pla-expressing Yersinia pestis and Escherichia coli K12 more efficiently than Pla-negative controls. The interactions between Pla-expressing bacteria and DEC-205-expressing transfectants or alveolar macrophages can be inhibited by an anti-DEC-205 antibody. The blockage of the Pla-DEC-205 interaction reduces the dissemination of Yersinia pestis in mice
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
plasminogen activator is upregulated at 37°C with calcium (2.4fold) and at 37°C without Ca2+ (2.8fold) compared to the case at 26°C with calcium
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Aprotinin
inhibits the recombinant enzyme expressed in Escherichia coli strain BL21 or DELTAcroP mutant strain of Citrobacter rodentium, in vivo. Docking model of the aprotinin-omptin complex. Lys15 of aprotinin interacts with Glu27 and Asp208 (OmpT numbering), which are the two negatively charged residues that form the S1 specificity pocket of omptins
additional information
-
WSLLTPAand YPYIPLT inhibit laminin binding activity of plasmonogen activator
-
additional information
potential small-peptide inhibitors of plasminogen activator Pla screened by parallel synthesis and positional scanning, selected small-peptide substrates analyzed by examining ability to inhibit the conversion of plasminogen to plasmin in a fibrin plate assay and by application of a fluorimetric assay
-
additional information
-
potential small-peptide inhibitors of plasminogen activator Pla screened by parallel synthesis and positional scanning, selected small-peptide substrates analyzed by examining ability to inhibit the conversion of plasminogen to plasmin in a fibrin plate assay and by application of a fluorimetric assay
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
bacterial lipopolysaccharide
-
LPS is required for the enzymatic activity of omptins, and in particular, LPS with short O-antigen side chains (rough LPS) is required for omptin activity toward many exogenous macromolecular substrates. It is thought that an extended O-antigen side chain (smooth LPS) sterically interferes with substrate binding
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0035
human Glu-plasminogen
-
pH not specified in the publication, temperature not specified in the publication
-
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
expression of Lpa gene shown in exponential and stationary growth phase, transcription shown to be directed by own promoter
additional information
kinetics of infection summarized, lack of plasminogen activator Pla shown to delay the time to death resulting from respiratory infection of mice, plasminogen activator Pla shown to control proliferation of Yersinia pestis in the lungs but is not essential for bacteria to disseminate, aborted inflammation and activated lung repair shown in absence of expression of plasminogen activator Pla
additional information
-
kinetics of infection summarized, lack of plasminogen activator Pla shown to delay the time to death resulting from respiratory infection of mice, plasminogen activator Pla shown to control proliferation of Yersinia pestis in the lungs but is not essential for bacteria to disseminate, aborted inflammation and activated lung repair shown in absence of expression of plasminogen activator Pla
additional information
peptide synthesis described, DABCYL/EDANS quencher/fluorophor system used, minimal substrate length determined, positional scan approach applied, peptide sequences tested as substrates and functional inhibitors listed, kinetics of cleavage of identified fluorescent substrates shown, fluorimetric assay and fibrinolytic assay applied, analysis of six-residue peptides and optimization studies of potential tripeptide substrates performed, inhibitory activity od selectetes small-peptides analyzed
additional information
-
peptide synthesis described, DABCYL/EDANS quencher/fluorophor system used, minimal substrate length determined, positional scan approach applied, peptide sequences tested as substrates and functional inhibitors listed, kinetics of cleavage of identified fluorescent substrates shown, fluorimetric assay and fibrinolytic assay applied, analysis of six-residue peptides and optimization studies of potential tripeptide substrates performed, inhibitory activity od selectetes small-peptides analyzed
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
26 - 37
-
plasminogen activator is upregulated at 37°C with calcium (2.4fold) and at 37°C without Ca2+ (2.8fold) compared to the case at 26°C with calcium
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
intracellularly grown in Acanthamoeba castellanii ATCC 30234
-
-
brenda
intracellularly grown in Acanthamoeba castellanii ATCC 30234
-
-
brenda
-
-
-
brenda
expression of Pla enhances bacterial adhesiveness to basement membranes and to laminin
-
-
brenda
non-pigmented avirulent strain of Yersinia pestis KIM, substrain D28, expressing plasminogen activator Pla and its pPCP-cured version, substrain D47
SwissProt
brenda
Pla mediates bacterial invasion into human endothelial cells independently of its proteolytic activity
-
-
brenda
wild-type strain CO92, isogenic strain lacking Pla (CO92 DELTA-pla) and complemented CO92 DELTA-pla strain
SwissProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
plasminogen is an abundant circulating zymogen of the serine protease plasmin, which is the key enzyme in fibrinolysis. The physiological plasminogen activation by uPA (EC 3.4.21.73) or tPA (EC 3.4.21.68) is a single cut at the peptide bond R560-V561, which yields the two-chain active plasmin enzyme. Pla rapidly cleaves the same peptide as do the human physiological activators, and the formed plasmin remains enzymatically active as Pla does not degrade the B chain of plasmin that contains the protease catalytic domain
physiological function
additional information
evolution
the pathogenicity factor is absent in representatives of the Yersinia pestis subsp. microtus bv. caucasica/SNP-type 0.PE2, while an ancestral Pla isoform (I259) with characteristics similar to the properties of omptins from less virulent enterobacteria is found in three representatives of Yersinia pestis subsp. microtus (SNP-types 0.PE3 and 0.PE4), which are, as a rule, avirulent to guinea pigs and humans. The modern isoform of Pla (T259) with an increased protease activity is found in Yersinia pestis subsp. pestis strains that are highly virulent for humans. Sequencing of pla genes from 118 Yersinia pestis subsp. microtus isolates reveals the absence of this gene in the strains belonging to bv. caucasica. All remaining isolates of Yersinia pestis subsp. microtus contain the ancestral Pla isoform (I259). Distribution of Pla isoforms among natural isolates of Yersinia pestis of different origin, overview
evolution
the modern isoform of Pla (T259) with an increased protease activity is found in Yersinia pestis subsp. pestis strains that are highly virulent for humans. The pathogenicity factor is absent in representatives of the Yersinia pestis subsp. microtus bv. caucasica/SNP-type 0.PE2, while an ancestral Pla isoform (I259) with characteristics similar to the properties of omptins from less virulent enterobacteria is found in three representatives of Yersinia pestis subsp. microtus (SNP-types 0.PE3 and 0.PE4), which are, as a rule, avirulent to guinea pigs and humans. Distribution of Pla isoforms among natural isolates of Yersinia pestis of different origin, overview
evolution
comparative analysis of the sequences of the pro-omptin Pla with other omptin family proteases, such as PgtE from Salmonella enterica (EC 3.4.23.49), SopA from Shigella flexneri, and OmpT and OmpP from Escherichia coli reveals the location of predicted linear B-cell epitopes in either identical positions or in a very close proximity to all nine Pla epitopes predicted from library, and identified serologically using human anti-Pla antisera, overview
evolution
-
the pathogenicity factor is absent in representatives of the Yersinia pestis subsp. microtus bv. caucasica/SNP-type 0.PE2, while an ancestral Pla isoform (I259) with characteristics similar to the properties of omptins from less virulent enterobacteria is found in three representatives of Yersinia pestis subsp. microtus (SNP-types 0.PE3 and 0.PE4), which are, as a rule, avirulent to guinea pigs and humans. The modern isoform of Pla (T259) with an increased protease activity is found in Yersinia pestis subsp. pestis strains that are highly virulent for humans. Sequencing of pla genes from 118 Yersinia pestis subsp. microtus isolates reveals the absence of this gene in the strains belonging to bv. caucasica. All remaining isolates of Yersinia pestis subsp. microtus contain the ancestral Pla isoform (I259). Distribution of Pla isoforms among natural isolates of Yersinia pestis of different origin, overview
-
evolution
-
comparative analysis of the sequences of the pro-omptin Pla with other omptin family proteases, such as PgtE from Salmonella enterica (EC 3.4.23.49), SopA from Shigella flexneri, and OmpT and OmpP from Escherichia coli reveals the location of predicted linear B-cell epitopes in either identical positions or in a very close proximity to all nine Pla epitopes predicted from library, and identified serologically using human anti-Pla antisera, overview
-
malfunction
-
eliminating Pla expression in a fully virulent Yersinia pestis strain decreases its LD50 by 6 orders of magnitude in a mouse model of bubonic plague
malfunction
-
Pla deficient Yersinia pestis disseminate to regional lymph nodes after subcutaneous inoculation but do not cause the lymphadenopathy observed with wild-type Yersinia pestis infections
malfunction
-
survival of mice infected with Pla-deficient Yersinia pestis is greater than cohorts infected with wild-type Yersinia Pestis. Survival advantage is negated, if fibrinogen knockout mice are infected instead, directly implicating the host coagulation system as a target for Pla's role in virulence
malfunction
deletion of Pla results in a decreased Yersinia pestis bacterial burden in the host lung and failure to progress into the lethal proinflammatory phase of disease. Deletion of Pla does not alter adherence to and/or secretion into THP-1 cells. Infection of human precision-cut lung slices (hPCLS) with the knockout DELTApla strain results in significantly reduced Yersinia outer protein (Yop) translocation early after infection and continuing to 4 hours-post-infection. And deletion of Pla results in decreased Yersinia pestis T3S into alveolar macrophages in vivo during pneumonic plague. Addition of Pla to Yersinia pestis lacking all five known adhesins partially restores adherence and Yop delivery to macrophages derived from the human monocytic cell line THP-1 and human epithelial type 2 (HEp-2) cells, suggesting that Pla may contribute to adherence and Yop translocation in vitro
malfunction
introducing the single point mutation D206A into the active site of Pla suffices to render fully virulent Yersinia pestis susceptible to primed T-cells
malfunction
Yersinia pestis D27
-
introducing the single point mutation D206A into the active site of Pla suffices to render fully virulent Yersinia pestis susceptible to primed T-cells
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physiological function
-
1. Pla expression results in attenuated inflammatory cell recruitment (particularly neutrophils) to infected lesions 2. Pla expression causes a structural derangement of infected lymph tissue characterized by lymphadenitis, necrosis, hemorrhage, thrombosis, and disorganized masses of infiltrating bacteria. 3. Pla expression promotes the systemic dissemination of the infection
physiological function
-
Pla works to accelerate the initiation phase of blood clotting by activating the first enzyme in blood clotting (factor VIIa) and inactivating its most important protease inhibitor in plasma (TFPI). This is highly reminiscent of the ability of Pla to activate plasminogen to plasmin and to inactivate its plasma inhibitor, alpha2-antiplasmin
physiological function
-
Yersinia pestis binding to fibronectin is mediated through Ail protein and plasminogen activator Pla
physiological function
-
the outer membrane plasminogen activator Pla of Yersinia pestis is a central virulence factor in plague
physiological function
-
the plasminogen activator Pla single and the Braun lipoprotein Lpp Pla double mutant are unable to survive efficiently in murine and human macrophages. The levels of Pla and its associated protease activity are not affected in the Lpp single mutant, and, likewise, deletion of the Pla gene from wild-type does not alter Lpp levels. The ability of the Lpp Pla double mutant to be phagocytized by macrophages, to stimulate production of tumor necrosis factor-alpha and interleukin-6, and to activate the nitric oxide killing pathways of the host cells remains unaltered when compared to the wild-type-infected macrophages. Macrophages infected with either the wild-type or the Lpp Pla double mutant are equally efficient in their uptake of zymosan particles
physiological function
cleavage of Yersinia pestis autotransporter YapE by protease Pla is required to mediate bacterial aggregation and adherence to eukaryotic cells. Post-translation modification of YapE appears to be specific to Yersinia pestis. It was acquired along with the acquisition ofplasmid pPCP1 during the divergence of Yersinia pestis from Yersinia pseudotuberculosis, and is the first evidence of a mechanism to regulate bacterial adherence
physiological function
the activity of the plasminogen activator protease Pla is the key to the progression of infection of Yersinia pestis in humans. Enzyme Pla facilitates type 3 secretion into primary alveolar macrophages but not into the commonly used THP-1 cell line. Analysis of the role of Pla in promoting optimal type 3 secretion using primary human tissue with relevant host cell heterogeneity in human precision-cut lung slices, a model of living tissue. Pla is a key player in the early host/pathogen interactions and a key virulence factor. Pla plays a role in adherence to alveolar macrophages that may not be detected using immortalized cell lines
physiological function
the plasminogen activator Pla is a protease that promotes fibrin degradation and prevents T cell-mediated defense against fully virulent Yersinia pestis. Pla functions to thwart fibrin-dependent T-cell-mediated defense against plague by promoting fibrinolysis. The presence of primed CD8 T-cells can suffice to protect against a lethal dose (LD) of a virulent Yersinia pestis strain rendered deficient in Pla activity in a fibrin-dependent manner
physiological function
-
plasminogen activator inhibitor-1 (PAI-1) is an in vivo target of the Pla protease in the lungs during pneumonic plague. PAI-1 is a key regulator of the pulmonary innate immune response and contributes to the regulation of cytokine production and promotion of neutrophil recruitment during Yerisnia pestis respiratory infection. The inactivation of PAI-1 by Yersinia pestis alters the host environment to promote virulence. PAI-1 restricts the proliferation of Yersinia pestis in the absence of enzyme Pla
physiological function
Pla of the enteropathogen Yersinia pestis is a surface-exposed, transmembrane beta-barrel proteases of the omptin family that exhibit a complex array of interactions with the hemostatic systems in vitro, the protease is an established virulence factor. Pla favors fibrinolysis by direct activation of plasminogen, inactivation of the serpins plasminogen activator inhibitor-1 and alpha2-antiplasmin, inactivation of the thrombin-activable fibrinolysis inhibitor, and activation of single-chain urokinase. Inactivation of alpha2AP enables proteolysis by the Pla-generated plasmin. The enzymatic activity of the protease is strongly influenced by the environment-induced variations in lipopolysaccharide that binds to the beta-barrel. The protease cleaves the tissue factor pathway inhibitor and thus also expresses procoagulant activity. Some of the functions observed for Pla, such as adhesiveness to laminin and invasiveness into human cells as well as efficient plasmin generation are not shown by PgtE (EC 3.4.23.49) or OmpT. Pla is adapted to support efficient plasminogen activation in the bubonic plague and to enhance bacterial survival in the lungs
physiological function
Pla functions as an adhesin independent of its proteolytic function to suppress early neutrophil influx into the lungs, and Pla enzymatic activity contributes to bacterial resistance to neutrophil-mediated bacterial killing, i.e facilitates T3S and suppresses early neutrophil influx. Pla proteolytic activity is necessary for Yersinia pestis survival in the presence of neutrophils
physiological function
Yersinia pestis D27
-
the plasminogen activator Pla is a protease that promotes fibrin degradation and prevents T cell-mediated defense against fully virulent Yersinia pestis. Pla functions to thwart fibrin-dependent T-cell-mediated defense against plague by promoting fibrinolysis. The presence of primed CD8 T-cells can suffice to protect against a lethal dose (LD) of a virulent Yersinia pestis strain rendered deficient in Pla activity in a fibrin-dependent manner
-
physiological function
-
plasminogen activator inhibitor-1 (PAI-1) is an in vivo target of the Pla protease in the lungs during pneumonic plague. PAI-1 is a key regulator of the pulmonary innate immune response and contributes to the regulation of cytokine production and promotion of neutrophil recruitment during Yerisnia pestis respiratory infection. The inactivation of PAI-1 by Yersinia pestis alters the host environment to promote virulence. PAI-1 restricts the proliferation of Yersinia pestis in the absence of enzyme Pla
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additional information
the primary action of Pla is to protect bacteria from destruction rather than to alter the tissue environment to favor Yersinia pestis propagation in the host. Analysis of intraspecies distribution, intrinsic disorder propensity, and contribution to virulence of the two isoforms of Yersinia pestis plasminogen activator Pla, overview. Survival curves of the endemic I259 Pla+ strains are similar to the parent Pla-negative variants, but significant difference in mean time to death post infection between the Pla- strains and their I259 Pla+ variants can be seen only in the isogenic set of Yersinia pestis subsp. pestis strains. An essential role for the outer membrane protease Pla evolution in Yersinia pestis bubonic infection exacerbation is suggested that is necessary for intensification of epidemic process from endemic natural focality with sporadic cases in humans to rapidly expanding epizootics followed by human epidemic outbreaks, local epidemics or even pandemics. Pla expression is associated with a marked ability to colonize the viscera and thus cause lethal infection upon administration by peripheral routes of infection, such as intradermal or subcutaneous. The Pla activity is not required to initiate lethal disease by intravenous injection, which provides immediate access to fixed macrophages lining the capillary beds of the liver and spleen. Virulence study of Yersinia pestis expressing different isoforms of Pla in a bubonic plague model
additional information
the primary action of Pla is to protect bacteria from destruction rather than to alter the tissue environment to favor Yersinia pestis propagation in the host. Analysis of intraspecies distribution, intrinsic disorder propensity, and contribution to virulence of the two isoforms of Yersinia pestis plasminogen activator Pla, overview. Survival curves of the endemic I259 Pla+ strains are similar to the parent Pla-negative variants, but significant difference in mean time to death post infection between the Pla- strains and their I259 Pla+ variants can be seen only in the isogenic set of Yersinia pestis subsp. pestis strains. Pla expression is associated with a marked ability to colonize the viscera and thus cause lethal infection upon administration by peripheral routes of infection, such as intradermal or subcutaneous. The Pla activity is not required to initiate lethal disease by intravenous injection, which provides immediate access to fixed macrophages lining the capillary beds of the liver and spleen. Virulence study of Yersinia pestis expressing different isoforms of Pla in a bubonic plague model
additional information
-
the primary action of Pla is to protect bacteria from destruction rather than to alter the tissue environment to favor Yersinia pestis propagation in the host. Analysis of intraspecies distribution, intrinsic disorder propensity, and contribution to virulence of the two isoforms of Yersinia pestis plasminogen activator Pla, overview. Survival curves of the endemic I259 Pla+ strains are similar to the parent Pla-negative variants, but significant difference in mean time to death post infection between the Pla- strains and their I259 Pla+ variants can be seen only in the isogenic set of Yersinia pestis subsp. pestis strains. An essential role for the outer membrane protease Pla evolution in Yersinia pestis bubonic infection exacerbation is suggested that is necessary for intensification of epidemic process from endemic natural focality with sporadic cases in humans to rapidly expanding epizootics followed by human epidemic outbreaks, local epidemics or even pandemics. Pla expression is associated with a marked ability to colonize the viscera and thus cause lethal infection upon administration by peripheral routes of infection, such as intradermal or subcutaneous. The Pla activity is not required to initiate lethal disease by intravenous injection, which provides immediate access to fixed macrophages lining the capillary beds of the liver and spleen. Virulence study of Yersinia pestis expressing different isoforms of Pla in a bubonic plague model
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). A0A141BQM9_YERPE
312
0
34623
TrEMBL
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
31000
-
plasminogen activator Pla exhibits three molecular forms: alpha-Pla with an MW of 35000 Da, beta-Pla of 33000 Da and gamma-Pla with 31000 Da. the formation of beta-Pla from alpha-Pla results from autoprocessing at the residue Lys262. gamma-Pla most likely represents full-size mature Pla that has folded differently from alpha-Pla
32600
-
alpha-Pla, x * 32600, a transient 34600 Da primary Pla product is processed upon insertion into the outer membrane to yield alpha-Pla, deduced from nucleotide sequence
33000
-
plasminogen activator Pla exhibits three molecular forms: alpha-Pla with an MW of 35000 Da, beta-Pla of 33000 Da and gamma-Pla with 31000 Da. the formation of beta-Pla from alpha-Pla results from autoprocessing at the residue Lys262. gamma-Pla most likely represents full-size mature Pla that has folded differently from alpha-Pla
35000
-
plasminogen activator Pla exhibits three molecular forms: alpha-Pla with an MW of 35000 Da, beta-Pla of 33000 Da and gamma-Pla with 31000 Da. the formation of beta-Pla from alpha-Pla results from autoprocessing at the residue Lys262. gamma-Pla most likely represents full-size mature Pla that has folded differently from alpha-Pla
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
?
-
alpha-Pla, x * 32600, a transient 34600 Da primary Pla product is processed upon insertion into the outer membrane to yield alpha-Pla, deduced from nucleotide sequence
?
x * 36900, SDS-PAGE, x * 32600, about, unprocessed enzyme, sequence calculation, x * 29600, about, processed enzyme, sequence calculation
?
-
x * 36900, SDS-PAGE, x * 32600, about, unprocessed enzyme, sequence calculation, x * 29600, about, processed enzyme, sequence calculation
-
?
x * 34100, SDS-PAGE, x * 32600, about, unprocessed enzyme, sequence calculation, x * 29600, about, processed enzyme, sequence calculation
additional information
-
Pla occurs in 3 processed forms of alpha-Pla, beta-Pla and gamma-Pla, of which alpha-Pla with an apparant molecular mass of 37000 Da, corresponds to full-size mature Pla, and beta-Pla and gamma-Pla with molecular weights of 31000 Da and 35000 Da respectively, are thought to result from processing of alpha-Pla, beta-Pla may result from an autoprocessing event
additional information
-
Pla occurs in 3 processed forms of alpha-Pla, beta-Pla and gamma-Pla, of which alpha-Pla with an apparant molecular mass of 37000 Da, corresponds to full-size mature Pla, and beta-Pla and gamma-Pla with molecular weights of 31000 Da and 35000 Da respectively, are thought to result from processing of alpha-Pla, beta-Pla may result from an autoprocessing event
additional information
the Pla peptide has an atypical mobility on the protein gel
additional information
-
the Pla peptide has an atypical mobility on the protein gel
-
additional information
the Pla peptide has an atypical mobility on the protein gel
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
-
plasminogen activator Pla is autoprocessed at the C-terminus. This does not enhance plasminogen activation
proteolytic modification
the enzyme performs autoproteolysis
proteolytic modification
-
the enzyme performs autoproteolysis
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proteolytic modification
the enzyme performs autoproteolysis
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
co-crystal structure of lipopolysaccharide-free Pla in complex with the activation loop peptide of human plasminogen, its natural substrate. The structure shows that in the absence of lipopolysaccharide, the peptide substrate binds deep within the active site groove and displaces the nucleophilic water molecule, leading to inactivation
comparison of the structure of Pla and the modeled structure of protease Epo of the plant pathogenic Erwinia pyrifoliae
molecular dynamics simulation of interaction with plasminogen. After a total of 8 ns, the predicted docked complex of plasminogen-palsminogen activator Pla shows the relaxation of the beta-barrel structure of Pla and the progressive approximation and stabilization between the cleavage site of plasmnogen into the extracellular loops of Pla, followed by the increase in the number of H bonds
-
wild-type, to 1.9 A, and inactive mutant D86A, to 2.5 A resolution, respectively. The structure shows a water molecule located between active site residues D84 and H208, and a number of other water molecules. The R211 side-chain in loop L4 is close to the nucleophilic water and possibly involved in the stabilization of the oxyanion intermediate. Subtle conformational changes of H208 result from the binding of lipopolysaccharide to the outside of the barrel, explaining the unusual dependence of omptins on lipopolysaccharide for activity
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D206A
D86A
S99A
T259I
-
the substitution impairs fibrinolytic activity and plasminogen activation
D206A
Yersinia pestis D27
-
site-directed mutagenesis, introducing the single point mutation into the active site of Pla suffices to render fully virulent Yersinia pestis susceptible to primed T-cells. The protective capacity of YopE-specific CD8 T cells against CO92 Pla-D206A is abrogated in mice with low levels of tissue factor activity as well as in PAI-1/TAFI double knockout mice. In addition, YopE-specific CD8 T cells poorly protect wild-type mice treated with Coumadin, a pharmacologic anticoagulant that reduces production of fibrin
-
additional information
D206A
site-directed mutagenesis, introducing the single point mutation into the active site of Pla suffices to render fully virulent Yersinia pestis susceptible to primed T-cells. The protective capacity of YopE-specific CD8 T cells against CO92 Pla-D206A is abrogated in mice with low levels of tissue factor activity as well as in PAI-1/TAFI double knockout mice. In addition, YopE-specific CD8 T cells poorly protect wild-type mice treated with Coumadin, a pharmacologic anticoagulant that reduces production of fibrin
D206A
strain is as attenuated as a Pla deletion strain at 12 or 24 h after infection of mice
S99A
strain is as attenuated as a Pla deletion strain at 12 or 24 h after infection of mice
additional information
-
the acyltransferase gene mutant lpxM has an altered activity of plasminogen activator Pla
additional information
swapping of ten amino acid residues at two surface loops of Pla and membrane protease Epo of the plant pathogenic Erwinia pyrifoliae introduces plasminogen activation capacity in Epo and inactivates the function in Pla
additional information
the Pla I259T modification is not required to cause pneumonic plague in the murine intranasal model
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purification of a His6-tagged fusion protein from Escherichia coli and reconstitution with lipopolysaccharide to an enzymatically active form. Purified His-tagged enzyme is coated onto fluorescent micro-particles and expresses plasminogen activity. The enzyme molecules have intrinsic adhesive properties. The purified transmembrane proteins coated onto fluorescence micro-particles can be used for functional assays
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
BL21-DE3 used as a host to express recombinant protein, cloning into pBluescript SK+ to produce plasmid pBLA4L
expressed in Escherichia coli TG1, strains BL21 and BL21(DE3)pLys used for expression of recombinant proteins
-
expression in Escherichia coli
gene pla, recombinant expression in a DELTAcroP mutant strain of Citrobacter rodentium and in Escherichia coli strain BL21
Pla is encoded by the 9.5 kb Yersinia pestis plasmid pPCP, sequence comparisons
Pla is encoded by the 9.5 kb Yersinia pestis plasmid pPCP, sequencing of pla genes from 118 Yersinia pestis subsp. microtus isolates, sequence comparisons
tetracycline-responsive promoter system in Yersinia pestis applied to control primary pneumonic plague progression after activation/inhibition of plasminogen activator Pla expression
the mutant enzyme T259I is expressed in Escherichia coli XL1 Blue cells and in Yersinia pestis strain KIM D34
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
medicine
analysis
-
multiplex real-time polymerase chain reaction assay for the detection of Yersinia pestis and Yersinia pseudotuberculosis using the Yersinia pestis pla gene coding for plasminogen activator and the ypo2088 gene. Assays are both sensitive and specific, the lower detection limit is 10-100 fg of extracted total DNA
analysis
-
development of a highly sensitive one-step PLA-enzyme immunoassay and an immunostrip, usable as a rapid test under field conditions. The PLA-immunometric tests allow a rapid and easy detection of Yersinia pestis in environmental and flea samples
medicine
-
the Lpp Pla double mutant of Yersinia pestis CO92 is highly attenuated and it retains the ability to elicit innate and subsequent acquired immune responses in the host similar to that of wild-type CO92, which are highly desirable in a live-attenuated vaccine candidate
medicine
the enzyme is a target for vaccine development. B-cell epitope mapping with Human Sera, three-dimensional modeling, omptins allergenicity and antigenicity prediction, overviw
medicine
-
the enzyme is a target for vaccine development. B-cell epitope mapping with Human Sera, three-dimensional modeling, omptins allergenicity and antigenicity prediction, overviw
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kienle, Z.; Emody, L.; Svanborg, C.; O'Toole, P.W.
Adhesive properties conferred by the plasminogen activator of Yersinia pestis
J. Gen. Microbiol.
138
1679-1687
1992
Yersinia pestis
-
brenda
Lahteenmaki, K.; Virkola, R.; Saren, A.; Emody, L.; Korhonen, T.K.
Expression of plasminogen activator Pla of Yersinia pestis enhances bacterial attachment to the mammalian extracellular matrix
Infect. Immun.
66
5755-5762
1998
Yersinia pestis
brenda
Kutyrev, V.; Mehigh, R.J.; Motin, V.L.; Pokrovskaya, M.S.; Smirnov, G.B.; Brubaker, R.R.
Expression of the plague plasminogen activator in Yersinia pseudotuberculosis and Escherichia coli
Infect. Immun.
67
1359-1367
1999
Yersinia pestis
brenda
Lahteenmaki, K.; Kukkonen, M.; Korhonen, T.K.
The Pla surface protease/adhesin of Yersinia pestis mediates bacterial invasion into human endothelial cells
FEBS Lett.
504
69-72
2001
Yersinia pestis
brenda
Kukkonen, M.; Lahteenmaki, K.; Suomalainen, M.; Kalkkinen, N.; Emody, L.; Lang, H.; Korhonen, T.K.
Protein regions important for plasminogen activation and inactivation of a2-antiplasmin in the surface protease Pla of Yersinia pestis
Mol. Microbiol.
40
1097-1111
2001
Yersinia pestis
brenda
Lahteenmaki, K.; Kuusela, P.; Korhonen, T.K.
Bacterial plasminogen activators and receptors
FEMS Microbiol. Rev.
25
531-552
2001
Yersinia pestis, Mammalia, Streptococcus uberis, Mycobacterium tuberculosis
brenda
Benedek, O.; Bene, J.; Melegh, B.; Emody, L.
Mapping of possible laminin binding sites of Y. pestis plasminogen activator (Pla) via phage display
Adv. Exp. Med. Biol.
529
101-104
2003
Yersinia pestis
brenda
Lobo, L.A.
Adhesive properties of the purified plasminogen activator Pla of Yersinia pestis
FEMS Microbiol. Lett.
262
158-162
2006
Yersinia pestis
brenda
Korhonen, T.K.; Lahteenmaki, K.; Kukkonen, M.; Lang, H.
Plasminogen activator of Yersinia pestis
Handbook of proteolytic enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , eds. ) Academic Press
1
217-219
2004
Yersinia pestis
-
brenda
Benedek, O.; Khan, A.S.; Schneider, G.; Nagy, G.; Autar, R.; Pieters, R.J.; Emody, L.
Identification of laminin-binding motifs of Yersinia pestis plasminogen activator by phage display
Int. J. Med. Microbiol.
295
87-98
2005
Yersinia pestis
brenda
Chromy, B.A.; Choi, M.W.; Murphy, G.A.; Gonzales, A.D.; Corzett, C.H.; Chang, B.C.; Fitch, J.P.; McCutchen-Maloney, S.L.
Proteomic characterization of Yersinia pestis virulence
J. Bacteriol.
187
8172-8180
2005
Yersinia pestis
brenda
Benedek, O.; Nagy, G.; Emody, L.
Intracellular signalling and cytoskeletal rearrangement involved in Yersinia pestis plasminogen activator (Pla) mediated HeLa cell invasion
Microb. Pathog.
37
47-54
2004
Yersinia pestis
brenda
Agarkov, A.; Chauhan, S.; Lory, P.J.; Gilbertson, S.R.; Motin, V.L.
Substrate specificity and screening of the integral membrane protease Pla
Bioorg. Med. Chem. Lett.
18
427-431
2008
Yersinia pestis (P17811), Yersinia pestis
brenda
Vranckx, L.; De Buck, E.; Anne, J.; Lammertyn, E.
Legionella pneumophila exhibits plasminogen activator activity
Microbiology
153
3757-3765
2007
Legionella pneumophila, Legionella pneumophila Philadelphia
brenda
Lathem, W.W.; Price, P.A.; Miller, V.L.; Goldman, W.E.
A plasminogen-activating protease specifically controls the development of primary pneumonic plague
Science
315
509-513
2007
Yersinia pestis (P17811), Yersinia pestis
brenda
Matero, P.; Pasanen, T.; Laukkanen, R.; Tissari, P.; Tarkka, E.; Vaara, M.; Skurnik, M.
Real-time multiplex PCR assay for detection of Yersinia pestis and Yersinia pseudotuberculosis
APMIS
117
34-44
2009
Yersinia pestis
brenda
Zhang, S.S.; Park, C.G.; Zhang, P.; Bartra, S.S.; Plano, G.V.; Klena, J.D.; Skurnik, M.; Hinnebusch, B.J.; Chen, T.
Plasminogen activator Pla of Yersinia pestis utilizes murine DEC-205 (CD205) as a receptor to promote dissemination
J. Biol. Chem.
283
31511-31521
2008
Yersinia pestis
brenda
Yun, T.; Morrissey, J.
Polyphosphate and omptins: Novel bacterial procoagulant agents
J. Cell. Mol. Med.
13
4146-4153
2009
Yersinia pestis
brenda
Tsang, T.M.; Felek, S.; Krukonis, E.S.
Ail binding to fibronectin facilitates Yersinia pestis binding to host cells and Yop delivery
Infect. Immun.
78
3358-3368
2010
Yersinia pestis
brenda
Haiko, J.; Kukkonen, M.; Ravantti, J.J.; Westerlund-Wikstroem, B.; Korhonen, T.K.
The single substitution I259T, conserved in the plasminogen activator Pla of pandemic Yersinia pestis branches, enhances fibrinolytic activity
J. Bacteriol.
191
4758-4766
2009
Yersinia pestis
brenda
Feodorova, V.; Pankina, L.; Savostina, E.; Kuznetsov, O.; Konnov, N.; Sayapina, L.; Dentovskaya, S.; Shaikhutdinova, R.; Ageev, S.; Lindner, B.; Kondakova, A.; Kocharova, N.; Senchenkova, S.; Holst, O.; Pier, G.; Knirel, Y.; Anisimov, A.; Motin, V.
Yersinia pestis live vaccine with improved characteristics
Procedia Vaccinol.
1
97-100
2009
Yersinia pestis
-
brenda
Haiko, J.; Laakkonen, L.; Westerlund-Wikstroem, B.; Korhonen, T.K.
Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla
BMC Evol. Biol.
11
43
2011
Yersinia pestis (P17811)
brenda
Eren, E.; Murphy, M.; Goguen, J.; van den Berg, B.
An active site water network in the plasminogen activator pla from Yersinia pestis
Structure
18
809-818
2010
Yersinia pestis (P17811), Yersinia pestis
brenda
Eren, E.; Van Den Berg, B.
Structural basis for activation of an integral membrane protease by lipopolysaccharide
J. Biol. Chem.
287
23971-23976
2012
Yersinia pestis (P17811)
brenda
Ruback, E.; Lobo, L.A.; Franca, T.C.; Pascutti, P.G.
Structural analysis of Pla protein from the biological warfare agent Yersinia pestis: docking and molecular dynamics of interactions with the mammalian plasminogen system
J. Biomol. Struct. Dyn.
31
477-484
2013
Yersinia pestis
brenda
Lane, M.C.; Lenz, J.D.; Miller, V.L.
Proteolytic processing of the Yersinia pestis YapG autotransporter by the omptin protease Pla and the contribution of YapG to murine plague pathogenesis
J. Med. Microbiol.
62
1124-1134
2013
Yersinia pestis (P17811)
brenda
van Lier, C.J.; Tiner, B.L.; Chauhan, S.; Motin, V.L.; Fitts, E.C.; Huante, M.B.; Endsley, J.J.; Ponnusamy, D.; Sha, J.; Chopra, A.K.
Further characterization of a highly attenuated Yersinia pestis CO92 mutant deleted for the genes encoding Braun lipoprotein and plasminogen activator protease in murine alveolar and primary human macrophages
Microb. Pathog.
80
27-38
2015
Yersinia pestis
brenda
Lawrenz, M.B.; Pennington, J.; Miller, V.L.
Acquisition of omptin reveals cryptic virulence function of autotransporter YapE in Yersinia pestis
Mol. Microbiol.
89
276-287
2013
Yersinia pestis (P17811)
brenda
Simon, S.; Demeure, C.; Lamourette, P.; Filali, S.; Plaisance, M.; Creminon, C.; Volland, H.; Carniel, E.
Fast and simple detection of Yersinia pestis applicable to field investigation of plague foci
PLoS ONE
8
e54947
2013
Yersinia pestis
brenda
Brannon, J.R.; Burk, D.L.; Leclerc, J.M.; Thomassin, J.L.; Portt, A.; Berghuis, A.M.; Gruenheid, S.; Le Moual, H.
Inhibition of outer membrane proteases of the omptin family by aprotinin
Infect. Immun.
83
2300-2311
2015
Yersinia pestis (P17811)
brenda
Smiley, S.T.; Szaba, F.M.; Kummer, L.W.; Duso, D.K.; Lin, J.S.
Yersinia pestis Pla protein thwarts T cell defense against plague
Infect. Immun.
87
e00126-19
2019
Yersinia pestis (P17811), Yersinia pestis, Yersinia pestis D27 (P17811)
brenda
Banerjee, S.K.; Huckuntod, S.D.; Mills, S.D.; Kurten, R.C.; Pechous, R.D.
Modeling pneumonic plague in human precision-cut lung slices highlights a role for the plasminogen activator protease in facilitating type 3 secretion
Infect. Immun.
87
e00175-19
2019
Yersinia pestis (P17811), Yersinia pestis
brenda
Korhonen, T.K.
Fibrinolytic and procoagulant activities of Yersinia pestis and Salmonella enterica
J. Thromb. Haemost.
13 Suppl 1
S115-S120
2015
Yersinia pestis (P17811)
brenda
Eddy, J.L.; Schroeder, J.A.; Zimbler, D.L.; Caulfield, A.J.; Lathem, W.W.
Proteolysis of plasminogen activator inhibitor-1 by Yersinia pestis remodulates the host environment to promote virulence
J. Thromb. Haemost.
14
1833-1843
2016
Yersinia pestis, Yersinia pestis CO92
brenda
Dentovskaya, S.V.; Platonov, M.E.; Svetoch, T.E.; Kopylov, P.K.; Kombarova, T.I.; Ivanov, S.A.; Shaikhutdinova, R.Z.; Kolombet, L.V.; Chauhan, S.; Ablamunits, V.G.; Motin, V.L.; Uversky, V.N.; Anisimov, A.P.
Two isoforms of Yersinia pestis plasminogen activator Pla intraspecies distribution, intrinsic disorder propensity, and contribution to virulence
PLoS ONE
11
e0168089
2016
Yersinia pestis subsp. microtus (A0A141BQM9), Yersinia pestis subsp. pestis (P17811), Yersinia pestis subsp. microtus 91001 (A0A141BQM9)
brenda
Feodorova, V.A.; Lyapina, A.M.; Zaitsev, S.S.; Khizhnyakova, M.A.; Sayapina, L.V.; Ulianova, O.V.; Ulyanov, S.S.; Motin, V.L.
New promising targets for synthetic omptin-based peptide vaccine against Gram-negative pathogens
Vaccines (Basel)
7
36
2019
Yersinia pestis (P17811), Yersinia pestis CO92 (P17811)
brenda
Banerjee, S.K.; Crane, S.D.; Pechous, R.D.
A dual role for the plasminogen activator protease during the preinflammatory phase of primary pneumonic plague
J. Infect. Dis.
222
407-416
2020
Yersinia pestis (P17811)
brenda
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