Information on EC 3.4.23.48 - plasminogen activator Pla

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY hide
3.4.23.48
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RECOMMENDED NAME
GeneOntology No.
plasminogen activator Pla
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REACTION
REACTION DIAGRAM
COMMENTARY hide
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
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
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-
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CAS REGISTRY NUMBER
COMMENTARY hide
101028-08-4
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain Philadelphia, intracellularly grown in Acanthamoeba castellanii ATCC 30234
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Manually annotated by BRENDA team
strain Philadelphia, intracellularly grown in Acanthamoeba castellanii ATCC 30234
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Manually annotated by BRENDA team
tissue-type plasminogen activator and urokinase
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Manually annotated by BRENDA team
mechanism of plasminogen activation is not known
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
alpha2-antiplasmin + H2O
?
show the reaction diagram
C3 protein of complement system + H2O
fragments of C3 protein of complement system
show the reaction diagram
complement protein C3 + H2O
?
show the reaction diagram
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-
-
-
?
D-Val-Leu-Lys-p-nitroanilide + H2O
D-Val-Leu-Lys + p-nitroaniline
show the reaction diagram
human alpha2-antiplasmin + H2O
fragments of alpha2-antiplasmin
show the reaction diagram
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-
-
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PAI-1 + H2O
?
show the reaction diagram
a serpin
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-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
serpin alpha2-antiplasmin + H2O
?
show the reaction diagram
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-
-
-
?
YapE + H2O
?
show the reaction diagram
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Yersinia pestis autotransporter YapE protein
cleavage of YapE occurs in Yersinia pestis but not in the enteric Yersinia species, and requires the omptin Pla
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?
YapG + H2O
?
show the reaction diagram
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Yersinia pestis autotransporter YapG protein
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
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?
Yersinia outer proteins + H2O
fragments of Yersinia outer proteins
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
alpha2-antiplasmin + H2O
?
show the reaction diagram
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Pla inactivates alpha2-antiplasmin
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-
?
C3 protein of complement system + H2O
fragments of C3 protein of complement system
show the reaction diagram
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-
-
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human alpha2-antiplasmin + H2O
fragments of alpha2-antiplasmin
show the reaction diagram
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-
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plasminogen + H2O
plasmin + ?
show the reaction diagram
YapE + H2O
?
show the reaction diagram
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Yersinia pestis autotransporter YapE protein
cleavage of YapE occurs in Yersinia pestis but not in the enteric Yersinia species, and requires the omptin Pla
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?
YapG + H2O
?
show the reaction diagram
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Yersinia pestis autotransporter YapG protein
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
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?
Yersinia outer proteins + H2O
fragments of Yersinia outer proteins
show the reaction diagram
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-
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additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
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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
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
PAI-1
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inhibition of tissue-type plasminogen activator and urokinase
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PAI-2
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inhibition of urokinase
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additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000145
plasminogen
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0035
plasminogen
Yersinia pestis
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
26 - 37
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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
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
C57BL/6 mice infected with Yersinia pestis
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
31000
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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
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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
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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
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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
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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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
additional information
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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
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
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plasminogen activator Pla is autoprocessed at the C-terminus. This does not enhance plasminogen activation
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
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comparison of the structure of Pla and the modeled structure of protease Epo of the plant pathogenic Erwinia pyrifoliae
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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
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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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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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recombinant plasminogen activator Pla, gel filtration
recombinant protein, gel fitration
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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
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expression in Escherichia coli
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expression in Escherichia coli and Yersinia pseudotuberculosis
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expression of 9.5 kb plasmid harboring the Pla gene in Escherichia coli
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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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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D212R
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111% of wild-type plasminogen activation
D84A
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3.7% of wild-type plasminogen activation
D97A
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56% of wild-type plasminogen activation
E217S
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52% of wild-type plasminogen activation
F215Y
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42% of wild-type plasminogen activation
G178A/L179A
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mutation decreases laminin binding in the YPYIPTL region
H101V
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0.8% of wild-type plasminogen activation
H108V
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121% of wild-type plasminogen activation
H203V
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109% of wild-type plasminogen activation
H208V
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1.7% of wild-type plasminogen activation
H28V
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125% of wild-type plasminogen activation
H98V
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94% of wild-type plasminogen activation
K218A
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103% of wild-type plasminogen activation
K240A
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151% of wild-type plasminogen activation
K249A
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132% of wild-type plasminogen activation
K254A
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90% of wild-type plasminogen activation
K262A
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85% of wild-type plasminogen activation
K280A
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98% of wild-type plasminogen activation
L213I
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123% of wild-type plasminogen activation
L65A/T66A/L67A
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mutation decreases laminin binding in the WSLLTPA region
M210G
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58% of wild-type plasminogen activation
R211K
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11% of wild-type plasminogen activation
S267A
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108% of wild-type plasminogen activation
S77A
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133% of wild-type plasminogen activation
T259I
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the substitution impairs fibrinolytic activity and plasminogen activation
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
medicine
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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