Information on EC 3.4.24.29 - aureolysin

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The expected taxonomic range for this enzyme is: Staphylococcus aureus

EC NUMBER
COMMENTARY
3.4.24.29
-
RECOMMENDED NAME
GeneOntology No.
aureolysin
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Cleavage of insulin B chain with specificity similar to that of thermolysin, preferring hydrophobic P1' residue. Activates the glutamyl endopeptidase (EC 3.4.21.19) of Staphylococcus aureus
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Aur
Staphylococcus aureus RN4220
-
-
-
C3 convertase
-
-
C3 convertase
Staphylococcus aureus KV27
-
-
-
EC 3.4.24.4
-
-
formerly
-
EC 3.4.99.22
-
-
formerly
-
Proteinase, Staphylococcus aureus neutral
-
-
-
-
Staphylococcus aureus neutral protease
-
-
-
-
Staphylococcus aureus neutral proteinase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
39335-13-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
a clinical isolate
-
-
Manually annotated by BRENDA team
analysis of polymorphisms in vancomycin-resistant strains, VRS1, HIP11714, strain VRS2, HIP11983 and strain VRS3, HIP13170 reveals a high degree of gene polymorphism. The aur gene is subject to stronger purifying selection than the multilocus sequence typing genes MLST. Proper enzymatic activity and specificity of aureolysin is very important in the processing of other staphylococcal proteins
-
-
Manually annotated by BRENDA team
mutant of strain V8
-
-
Manually annotated by BRENDA team
strain 8325-4
-
-
Manually annotated by BRENDA team
strain A152
-
-
Manually annotated by BRENDA team
strain RN4220
-
-
Manually annotated by BRENDA team
strain V8-BC 10
-
-
Manually annotated by BRENDA team
strains 8325-4 and RN4220, gene aur
-
-
Manually annotated by BRENDA team
wild-type strain 8325-4, gene aur
-
-
Manually annotated by BRENDA team
wild-type strains 8325-4 and Newman, and clinical isolates
-
-
Manually annotated by BRENDA team
Staphylococcus aureus 8325-4
strain 8325-4
-
-
Manually annotated by BRENDA team
Staphylococcus aureus A152
strain A152
-
-
Manually annotated by BRENDA team
Staphylococcus aureus KV27
a clinical isolate
-
-
Manually annotated by BRENDA team
Staphylococcus aureus RN4220
strain RN4220
-
-
Manually annotated by BRENDA team
Staphylococcus aureus V8
strain V8
-
-
Manually annotated by BRENDA team
Staphylococcus aureus V8-BC
strain V8-BC 10
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
the sigB mutant strain overexpresses the surface-anchored protein Bap, that is essential for biofilm formation in the model strain. Staphylococcus aureus completely inhibits the biofilm formation of the mutant strain via Aur and SspA, two proteases that are overexpressed in the sigB mutant strain and are capable of degrading Bap
physiological function
-
Staphylococcus aureus metalloprotease aureolysin cleaves complement C3 to mediate immune evasion and is a potent complement inhibitor dependent on its proteolytic activity. Aureolysin effectively inhibits phagocytosis and killing of bacteria by neutrophils in the human host, e.g. in U937 cells, aureolysin inhibits C3b deposition and C5a generation, overview. Aureolysin is essential and sufficient for C3 cleavage by bacterial supernatant, but acts in synergy with host regulators to inactivate C3 thereby effectively dampening the host immune response. Aureolysin acts as a C3 convertase
physiological function
-
extracellular proteases Aur and SspA inhibit protein-dependent biofilm formation by Staphylococcus aureus, detailed overview
physiological function
Staphylococcus aureus KV27
-
Staphylococcus aureus metalloprotease aureolysin cleaves complement C3 to mediate immune evasion and is a potent complement inhibitor dependent on its proteolytic activity. Aureolysin effectively inhibits phagocytosis and killing of bacteria by neutrophils in the human host, e.g. in U937 cells, aureolysin inhibits C3b deposition and C5a generation, overview. Aureolysin is essential and sufficient for C3 cleavage by bacterial supernatant, but acts in synergy with host regulators to inactivate C3 thereby effectively dampening the host immune response. Aureolysin acts as a C3 convertase
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
alpha-toxin + H2O
?
show the reaction diagram
Staphylococcus aureus, Staphylococcus aureus Wood 46
-
-
-
-
?
alpha2-macroglobulin + H2O
?
show the reaction diagram
-
processing of the inhibitor, the initial N-terminal hydrolysis of alpha2-macroglobulin by aureolysin does not affect the serpin inhibitory activity, cleavage within its exposed reactive loop is associated with a decreased inhibitory activity, down to 23% of the control inhibitor
-
-
?
Bap + H2O
?
show the reaction diagram
-
a surface-anchored protein
-
-
?
casein + H2O
hydrolyzed casein
show the reaction diagram
-
-
-
-
-
casein + H2O
hydrolyzed casein
show the reaction diagram
Staphylococcus aureus V8
-
-
-
-
-
casein + H2O
hydrolyzed casein
show the reaction diagram
Staphylococcus aureus A152
-
-
-
-
-
cathelicidin LL-37 + H2O
?
show the reaction diagram
-
human antimicrobial peptide. Enzyme production by Staphylococcus aureus contributes to its resistance to the innate immune system of humans mediated by LL-37, human antimicrobial peptide, cleavage by enzyme at R19-I20, R23-I24, L31-V32
-
-
?
complement component C3 + H2O
C3a+SN + C3b2SN
show the reaction diagram
-
aureolysin cleaves purified C3 specifically in the alpha-chain, close to the C3 convertase cleavage site, yielding active C3a and C3b. In serum, the aureolysin-generated C3b is further degraded by host factors, aureolysin cleaves purified C3 specifically in the alpha-chain, close to the C3 convertase cleavage site, yielding active C3a and C3b
both products are active
-
?
complement component C3 + H2O
C3a+SN + C3b2SN
show the reaction diagram
Staphylococcus aureus KV27
-
aureolysin cleaves purified C3 specifically in the alpha-chain, close to the C3 convertase cleavage site, yielding active C3a and C3b. In serum, the aureolysin-generated C3b is further degraded by host factors, aureolysin cleaves purified C3 specifically in the alpha-chain, close to the C3 convertase cleavage site, yielding active C3a and C3b
both products are active
-
?
Gelatin + H2O
?
show the reaction diagram
-
-
-
-
?
GWTLNSAGYLLGPHAIDNHRSFHDKYGLA-NH2 + H2O
Gly-Trp-Thr + Leu-Asn-Ser + Ala-Gly + Tyr + Leu + LGPHAIDNHRS + FHDKYG + Leu-Ala-NH2
show the reaction diagram
-
i.e. galanin
-
-
?
Nalpha-furylacryloyl-Gly-Ala-NH2 + H2O
?
show the reaction diagram
-
very poor substrate
-
-
?
Nalpha-Furylacryloyl-Gly-Leu amide + H2O
?
show the reaction diagram
-
-
-
-
-
Nalpha-furylacryloyl-Gly-Leu-NH2
?
show the reaction diagram
-
Nalpha-furylacryloyl-Gly-Phe-NH2 is a better substrate than Fa-Gly-Leu-NH2
-
-
?
Nalpha-furylacryloyl-Gly-Phe-NH2
?
show the reaction diagram
-
Nalpha-furylacryloyl-Gly-Phe-NH2 is a better substrate than Fa-Gly-Leu-NH2
-
-
?
Nalpha-furylacryloyl-Gly-Val-NH2 + H2O
?
show the reaction diagram
-
very poor substrate
-
-
?
Oxidized insulin B-chain + H2O
Hydrolyzed oxidized insulin
show the reaction diagram
-
hydrolysis of bonds in which the NH2-group of hydrophobic amino acids is involved, no hydrolysis of Phe24-Phe25
-
-
-
Oxidized insulin B-chain + H2O
Hydrolyzed oxidized insulin
show the reaction diagram
-
cleaves at His5-Leu6, His10-Leu11, Ala14-Leu15, Tyr16-Leu17, Gly23-Phe24, Phe25-Tyr26
-
-
-
Oxidized insulin B-chain + H2O
Hydrolyzed oxidized insulin
show the reaction diagram
Staphylococcus aureus A152
-
hydrolysis of bonds in which the NH2-group of hydrophobic amino acids is involved, no hydrolysis of Phe24-Phe25
-
-
-
plasminogen + H2O
angiostatin + mini-plasminogen
show the reaction diagram
-
-
-
-
?
plasminogen activator inhibitor-1 + H2O
?
show the reaction diagram
-
processing of the inhibitor, the proteolytic degradation of PAI-1 by aureolysin is associated with a drastic decrease in its capacity to inhibit uPA, down to 7% of the inhibitory activity of the control PAI-1
-
-
?
pro-urokinase-type plasmin activator + H2O
2 chains of urokinase-type plasmin activator
show the reaction diagram
-
human substrate, activation by cleavage into two enzyme chains, activity by wild-type strains 8325-4 and Newman, and clinical isolates, overview, no activity with N-terminal enzyme substrate mutants, overview
-
-
?
SspA zymogen + H2O
?
show the reaction diagram
-
aureolysin is essential for activation of SspA zymogen, but the first step in processing of the N-terminal propeptide requires autocatalytic intramolecular cleavage at glutamine, aureolysin then processes at Leu58 and then Val69 to produce the first active molecules of mature SspA, which then feed back to promote efficient autocatalytic intermolecular processing of remaining zSspA at Glu65, mechanism, overview, SspA is a serine protease secreted by Staphylococcus aureus as inactive zymogen, aureolysin is essential for activation of SspA zymogen, but the first step in processing of the N-terminal propeptide requires autocatalytic intramolecular cleavage at glutamine, aureolysin then processes at Leu58 and then Val69 to produce the first active molecules of mature SspA, which then feed back to promote efficient autocatalytic intermolecular processing of remaining zSspA at Glu65
-
-
?
SspA zymogen + H2O
?
show the reaction diagram
Staphylococcus aureus RN4220
-
aureolysin is essential for activation of SspA zymogen, but the first step in processing of the N-terminal propeptide requires autocatalytic intramolecular cleavage at glutamine, aureolysin then processes at Leu58 and then Val69 to produce the first active molecules of mature SspA, which then feed back to promote efficient autocatalytic intermolecular processing of remaining zSspA at Glu65, mechanism, overview, SspA is a serine protease secreted by Staphylococcus aureus as inactive zymogen, aureolysin is essential for activation of SspA zymogen, but the first step in processing of the N-terminal propeptide requires autocatalytic intramolecular cleavage at glutamine, aureolysin then processes at Leu58 and then Val69 to produce the first active molecules of mature SspA, which then feed back to promote efficient autocatalytic intermolecular processing of remaining zSspA at Glu65
-
-
?
Hemoglobin + H2O
Hydrolyzed hemoglobin
show the reaction diagram
Staphylococcus aureus, Staphylococcus aureus V8
-
-
-
-
-
additional information
?
-
-
specificity for peptide bonds on the N-terminal side of large hydrophobic residues
-
-
-
additional information
?
-
-
protease II exhibits esterase activity, using N-benzoyl-L-Tyr ethyl ester as substrate, no activity of protease I
-
-
-
additional information
?
-
-
activates the precursor of another protease secreted by the same organism, staphylococcal protease
-
-
-
additional information
?
-
-
the aur null mutant strain causes the same immune reaction in mice as the wild-type strain, overview
-
-
-
additional information
?
-
-
aureolysin does not hydrolyze GKHKNKGKKNGKHNGWK and HKHGHGHGKHKNKGKKN
-
-
-
additional information
?
-
-
Aureolysin collaborates with host factors to inactivate C3b
-
-
-
additional information
?
-
Staphylococcus aureus V8
-
protease II exhibits esterase activity, using N-benzoyl-L-Tyr ethyl ester as substrate, no activity of protease I
-
-
-
additional information
?
-
Staphylococcus aureus KV27
-
Aureolysin collaborates with host factors to inactivate C3b
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
Bap + H2O
?
show the reaction diagram
-
a surface-anchored protein
-
-
?
cathelicidin LL-37 + H2O
?
show the reaction diagram
-
human antimicrobial peptide. Enzyme production by Staphylococcus aureus contributes to its resistance to the innate immune system of humans mediated by LL-37
-
-
?
SspA zymogen + H2O
?
show the reaction diagram
Staphylococcus aureus, Staphylococcus aureus RN4220
-
aureolysin is essential for activation of SspA zymogen, but the first step in processing of the N-terminal propeptide requires autocatalytic intramolecular cleavage at glutamine, aureolysin then processes at Leu58 and then Val69 to produce the first active molecules of mature SspA, which then feed back to promote efficient autocatalytic intermolecular processing of remaining zSspA at Glu65, mechanism, overview
-
-
?
complement component C3 + H2O
C3a+SN + C3b2SN
show the reaction diagram
Staphylococcus aureus, Staphylococcus aureus KV27
-
aureolysin cleaves purified C3 specifically in the alpha-chain, close to the C3 convertase cleavage site, yielding active C3a and C3b. In serum, the aureolysin-generated C3b is further degraded by host factors
both products are active
-
?
additional information
?
-
-
activates the precursor of another protease secreted by the same organism, staphylococcal protease
-
-
-
additional information
?
-
-
the aur null mutant strain causes the same immune reaction in mice as the wild-type strain, overview
-
-
-
additional information
?
-
Staphylococcus aureus, Staphylococcus aureus KV27
-
Aureolysin collaborates with host factors to inactivate C3b
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
slight stimulation of protease I
Ca2+
-
binds one mol Zn2+ and three mol Ca2+
Co2+
-
slight stimulation of protease I, protease II inactive in presence of
Co2+
-
reactivates 1,10-phenanthroline inactivated enzyme with 160% of the activity of the native enzyme
Pb2+
-
slight stimulation of protease I
Zn2+
-
reactivates 1,10-phenanthroline inactivated enzyme
Zn2+
-
binds one mol Zn2+ and three mol Ca2+
Mg2+
-
slight stimulation of protease I
additional information
-
Aur is a metalloprotease
additional information
-
metalloprotease
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,10-phenanthroline
-
-
Ag2+
-
protease II
alpha2-Macroglobulin
-
a regulatory serpin, the initial N-terminal hydrolysis of alpha2-macroglobulin by aureolysin does not affect the serpin inhibitory activity, cleavage within its exposed reactive loop is associated with a decreased inhibitory activity, down to 23% of the control inhibitor
-
Co2+
-
protease II inactive in presence of, protease I slightly stimulated
Cu2+
-
protease II
DFP
-
1.0 mM, 30 min, 20°C, activity of protease I is reduced by 10%, activity of protease II by 30%
Hg2+
-
protease II
NaCl
-
50% reduction of activity at 0.3 M for protease I and 0.5 M for protease II
plasminogen activator inhibitor-1
-
PAI-1, a regulatory serpin, interaction analysis with aureolysin, overview, the proteolytic degradation of PAI-1 by aureolysin is associated with a drastic decrease in its capacity to inhibit uPA, down to 7% of the inhibitory activity of the control PAI-1
Zn2+
-
protease II
Mn2+
-
protease II
additional information
-
protease I is not significantly affected by SH-reducing, SH-inactivating or metal-complexing agents
-
additional information
-
no effect: reagents for serine enzymes
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Reducing agents
-
protease II active only in presence of reducing agents such as cysteine, 2-mercaptoethanol or sodium thioglycollate
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
additional information
-
additional information
-
kinetics
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
-
-
and 7.0-9.0, hemoglobin, protease I
7
9
-
and 5.0, hemoglobin, protease I
7
-
-
N-alpha-furylacryloyl-Gly-Leu amide
7.4
7.8
-
assay at
7.4
-
-
assay at
7.8
-
-
casein, protease I
8.8
-
-
casein, protease II
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
aureolysin is secreted
-
Manually annotated by BRENDA team
-
the enzyme is secreted
-
Manually annotated by BRENDA team
Staphylococcus aureus KV27
-
the enzyme is secreted
-
-
Manually annotated by BRENDA team
Staphylococcus aureus V8
-
-
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
12500
-
-
Staphylococcus aureus, protease II, gel filtration
21000
-
-
Staphylococcus aureus, protease I, gel filtration
26800
-
-
Staphylococcus aureus, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 38000, Staphylococcus aureus, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
proteolytic modification
-
mutation T85R/L86Y at the site of autocatalytic activation in the propeptide results in secretion of an intact N-terminal propeptide with degradation of the M4 metalloprotease domain. The fungalysin-thermolysin-propeptide domain promotes intracellular processing of proaureolysin while bestowing a chaperone function
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
inhibitor-free form, cristall from sitting-drop vapour-diffusion method, refinement by molecular replacement
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
11
-
37°C, 3 h, protease I stable
7
-
-
37°C, 3 h, 47% loss of activity, protease II
8
-
-
37°C, 3 h, 74% loss of activity, protease II
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
pH 4.0-11.0, 3 h, protease I stable
45
-
-
pH 7.0, 30 min, stable up to, protease I
50
-
-
pH 7.0, 30 min, 90% loss of activity, protease II
65
-
-
20 min, purified enzyme, inactivation
90
-
-
pH 7.0, 30 min, complete inactivation, protease I
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Purified enzyme contains trace amounts of a serine proteinase which rapidly degrades the Staphylococcus aureus metalloproteinase when EDTA is present, no degradation occurs when Ca2+ is added
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
native enzyme by hydrophobic interaction and ion exchange chromatography
-
protease I (pI: 4.0) and protease II (pI: 9.4)
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
gene aur, encoding the enzyme, is regulated by the genes sarA, rot, and agr, the latter encoding RNAIII, agr and mgr A stimulate enzyme expression, while rot and sar A suppress it, mutational analysis and expression analysis, overview
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
T85R/L86Y
-
mutation at the site of autocatalytic activation in the propeptide. Mutation results in secretion of an intact N-terminal propeptide with degradation of the M4 metalloprotease domain. The segment of the fungalysin-thermolysin-propeptide domain promotes intracellular processing of proaureolysin while bestowing a chaperone function
additional information
-
construction of aur- mutants lacking aureolysin activity
additional information
-
construction of diverse mutant strains using wild-type strain 8325-4, overview
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
enzyme does not act as a virulence factor. Staphylococcus aureus strains lacking enzyme, or serine protease, or cysteine protease, show similar frequency or severity of joint disease as wild-type in a mouse model
medicine
Staphylococcus aureus 8325-4
-
enzyme does not act as a virulence factor. Staphylococcus aureus strains lacking enzyme, or serine protease, or cysteine protease, show similar frequency or severity of joint disease as wild-type in a mouse model
-