Information on EC 3.4.24.34 - neutrophil collagenase and Organism(s) Homo sapiens

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Homo sapiens


The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.24.34
-
RECOMMENDED NAME
GeneOntology No.
neutrophil collagenase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
9001-12-1
not distinguishable from EC 3.4.24.3 and EC 3.4.24.7 in Chemical Abstracts
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
abrogation of MMP-8 activity by specific inhibitors as well as transfection with MMP-8 siRNA abolishes production of the cleavage fragment and occludin remained attached to the cell periphery
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
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly-norvaline-His-Ala-Arg-NH2 + H2O
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly + Nva-His-Ala-Arg-NH2
show the reaction diagram
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-diaminopropionyl-Ala-Arg-NH2 + H2O
?
show the reaction diagram
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-N-3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl-Ala-Arg-NH2 + H2O
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly + Leu-N3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl-Ala-Arg-NH2
show the reaction diagram
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-[3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl]-Ala-Arg-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
alpha1-proteinase inhibitor + H2O
?
show the reaction diagram
-
-
-
-
?
bovine collagen I + H2O
?
show the reaction diagram
cartilage aggrecan + H2O
?
show the reaction diagram
-
-
-
?
Cartilage aggrecan + H2O
hydrolyzed cartilage aggrecan
show the reaction diagram
-
cleavage at Glu373-Ala374 "aggrecanase" site in intraglobular domain
-
-
Collagen + H2O
?
show the reaction diagram
Dnp-Pro-Gln-Gly-Ile-Ala-Gly-Gln-(D)-Arg + H2O
?
show the reaction diagram
-
-
-
-
-
estrogen receptor alpha + H2O
?
show the reaction diagram
-
-
-
-
?
estrogen receptor beta + H2O
?
show the reaction diagram
-
-
-
-
?
Fibrillar type I collagen + H2O
?
show the reaction diagram
-
from human or guinea pig
-
-
-
Fibrillar type III collagen + H2O
?
show the reaction diagram
-
-
-
-
-
M-1855 + H2O
?
show the reaction diagram
-
-
-
?
Mca-Lys-Pro-Leu-Gly + H2O
?
show the reaction diagram
-
-
-
-
?
Monomeric type I collagen + H2O
collagen type I fragment TCA + collagen type I fragment TCB
show the reaction diagram
Monomeric type II collagen + H2O
collagen type II fragment TCA + collagen type II fragment TCB
show the reaction diagram
Monomeric type III collagen + H2O
collagen type III fragment TCA + collagen type III fragmentTCB
show the reaction diagram
TNF-alpha + H2O
?
show the reaction diagram
-
-
MMP8 exhibits TNF-alpha-converting enzyme activity by cleaving the prodomain of TNF-alpha at residues A74-Q75 and A76-V77
-
?
type 1 collagen + H2O
?
show the reaction diagram
-
degradation, production of 3/4(alphaA)-cleavage products
-
-
?
Type I collagen + H2O
?
show the reaction diagram
type III collagen + H2O
?
show the reaction diagram
additional information
?
-
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
Collagen + H2O
?
show the reaction diagram
estrogen receptor alpha + H2O
?
show the reaction diagram
-
-
-
-
?
estrogen receptor beta + H2O
?
show the reaction diagram
-
-
-
-
?
Type I collagen + H2O
?
show the reaction diagram
type III collagen + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1R)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]carboxylate
-
-
(1R)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]hydroxamate
-
-
(1R)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate
-
binding structure at the S1' pocket, detailed mode of binding, overview
(1S)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]carboxylate
-
-
(1S)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]hydroxamate
-
-
(1S)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate
-
binding structure at the S1' pocket, detailed mode of binding, overview
(2R,S)-HONH-Mal(Me/Bn)-1,2,9,10-tetrahydroisoquinolide
-
-
(2R,S)-HONH-Mal(Me/Bn)-alpha-naphthylamide
-
-
(2R,S)-HONH-Mal(Me/Bn)-NH-CH2CH2-Ph
-
-
(2R,S)-HONH-Mal(Me/Bn)-NH-CH2CH2CH2-Ph
-
-
(2R,S)-HONH-Mal(Me/Bn)-NH-CH2CH2CH2CH2-Ph
-
-
(2R,S)-HONH-Mal(Me/Bn)-NHBn
-
-
(2R,S)-HONH-Mal(Me/Bn)-NHBn-(p-COOH)
-
-
(2R,S)-HONH-Mal(Me/Bn)-NHPh
-
-
(2R,S)-HONH-Mal(Me/Bn)-Oet
-
-
(2R,S)-HONH-Mal(Me/i-Bu)-Oet
-
-
(2R,S)-HONH-Mal(NHAc/Bn)-NHBn
-
-
(2R,S)-HONH-Mal(OH/Bn)-NHBn
-
-
(2S,3R)-2-methyl-3-(2-methylpropyl)-1-(N-hydroxy)-4-(O-methyl)-L-tyrosine-N-methylamide
-
BB-16
(N-1(R)-carboxyethyl)-alpha-(S)-(4-phenyl-3-butynyl)glycyl-L-O-methyltyrosine, N-methylamide
-
SA751
(R)-2-(biphenyl-4-ylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-3-carboxylic acid
-
-
(R)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl] phosphonate
-
stereoselectivity, binding structure, molecular dynamic simulations of inhibitor bound to MMP-8, the 144-155 loop of the enzyme undergoes a drastic decrease of mobility once complexed with the enantiomer, overview
(S)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl] phosphonate
-
stereoselectivity, binding structure, molecular dynamic simulations of inhibitor bound to MMP-8, the 144-155 loop of the enzyme undergoes a drastic decrease of mobility once complexed with the enantiomer, overview
1,10-phenanthroline
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2-(arylsulfonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
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2-(arylsulfonyl)-1,2,3,4-tetrahydroisoquinoline-3-hydroxamate
-
-
batimastat
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BB-94, peptidomimetic MMP inhibitor
BB-1909
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-
EDTA
-
-
GM6001
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an MMP inhibitor
HONH-iBM-L-Ala-Gly-NH2
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-
HONH-iBM-L-Ala-NHBn
-
-
HONH-iBM-L-Asn-NHBn
-
-
HONH-iBM-L-Asn-NHBn(m-NH2)
-
-
HONH-iBM-L-Asp-NHBn
-
-
HONH-iBM-NH-(CH2)7CH3
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-
I-COL 043
-
-
Ile-Pro-Glu-Asn-Phe-Phe-Gly
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aggrecan as substrate
malonic acid hydroxamate
-
-
MMP-8 inhibitor I
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in the presence of specific MMP-8 I inhibitor formation of the occludin cleavage product is prevented
N-hydroxy-2-(2-[[4-(4-methoxyphenoxy)phenyl]sulfonyl]phenyl)acetamide
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-
N-hydroxy-N2-[(4'-methoxybiphenyl-4-yl)sulfonyl]-N2-(propan-2-yloxy)glycinamide
-
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N-hydroxy-N2-[(4-phenoxyphenyl)sulfonyl]-N2-(propan-2-yloxy)glycinamide
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N-hydroxy-N2-[(4-phenoxyphenyl)sulfonyl]valinamide
-
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N2-(biphenyl-4-ylsulfonyl)-N-hydroxy-N2-(propan-2-yloxy)glycinamide
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-
N2-(biphenyl-4-ylsulfonyl)-N-hydroxyglycinamide
-
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RO200-1770
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-
RO204-1924
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RO206-0027
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RO206-0032
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Thr-Glu-Gly-Glu-Ala-Arg-Gly
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aggrecan as substrate
TIMP-1
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TIMP-1 from brain is upregulated in in the infarcted tissue compared to healthy control areas, overview
-
TIMP-2
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highly produced in brain microvessels
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tissue inhibitor of matrix metalloproteinase-1
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i.e. TIMP-1, inhibits MMP-8. Elevated levels of TIMP-1 in blood are associated with poor prognosis in many cancers. Genotyping and identification of different single nucleotide polymorphisms in male and female patients of head and neck squamous cell carcinoma
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Tissue inhibitor of metalloproteinase-I
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i.e. TIMP-I
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
the enzyme expression is induced by estrogen
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0279 - 0.0622
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly-norvaline-His-Ala-Arg-NH2
0.0184 - 0.046
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-DIAMIONOPROPIONYL-Ala-Arg-NH2
0.0194 - 0.0465
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-L-diaminopropionyl-Ala-Arg-NH2
0.000208 - 14.4
bovine collagen I
0.0006
guinea pig collagen type I
-
37°C
-
0.0007
human collagen type I
-
37°C
-
0.0011
human collagen type II
-
37°C
-
0.0018
human collagen type III
-
37°C
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
180 - 570
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly-norvaline-His-Ala-Arg-NH2
145 - 522
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-diaminopropionyl-Ala-Arg-NH2
148 - 562
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-DIAMIONOPROPIONYL-Ala-Arg-NH2
0.0109 - 1120
bovine collagen I
0.00161
guinea pig collagen type I
-
37°C
-
0.00178
human collagen type I
-
37°C
-
0.00065
human collagen type II
-
37°C
-
0.000233
human collagen type III
-
37°C
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0081
(2R,S)-HONH-Mal(Me/Bn)-1,2,9,10-tetrahydroisoquinolide
-
pH 7.6, 25°C
0.045
(2R,S)-HONH-Mal(Me/Bn)-alpha-naphthylamide
-
pH 7.6, 25°C
0.0096
(2R,S)-HONH-Mal(Me/Bn)-NH-CH2CH2-Ph
-
pH 7.6, 25°C
0.00024
(2R,S)-HONH-Mal(Me/Bn)-NH-CH2CH2CH2-Ph
-
pH 7.6, 25°C
0.00038
(2R,S)-HONH-Mal(Me/Bn)-NH-CH2CH2CH2CH2-Ph
-
pH 7.6, 25°C
0.0011
(2R,S)-HONH-Mal(Me/Bn)-NHBn
-
pH 7.6, 25°C
0.041
(2R,S)-HONH-Mal(Me/Bn)-NHBn-(p-COOH)
-
pH 7.6, 25°C
0.044
(2R,S)-HONH-Mal(Me/Bn)-NHPh
-
pH 7.6, 25°C
0.011
(2R,S)-HONH-Mal(Me/Bn)-Oet
-
pH 7.6, 25°C
0.041
(2R,S)-HONH-Mal(Me/i-Bu)-Oet
-
pH 7.6, 25°C
0.0023
(2R,S)-HONH-Mal(NHAc/Bn)-NHBn
-
pH 7.6, 25°C
0.0019
(2R,S)-HONH-Mal(OH/Bn)-NHBn
-
pH 7.6, 25°C
0.0000007
(2S,3R)-2-methyl-3-(2-methylpropyl)-1-(N-hydroxy)-4-(O-methyl)-L-tyrosine-N-methylamide
-
pH 7.5, 37°C, BB-16
0.000002
(N-1(R)-carboxyethyl)-alpha-(S)-(4-phenyl-3-butynyl)glycyl-L-O-methyltyrosine, N-methylamide
-
pH 7.5, 37°C, SA751
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000006
(1R)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate
Homo sapiens
-
pH 7.5, 25°C
0.0007
(1S)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate
Homo sapiens
-
pH 7.5, 25°C
0.000005 - 0.000034
N-hydroxy-2-(2-[[4-(4-methoxyphenoxy)phenyl]sulfonyl]phenyl)acetamide
0.000065 - 0.00033
N-hydroxy-N2-[(4'-methoxybiphenyl-4-yl)sulfonyl]-N2-(propan-2-yloxy)glycinamide
0.000065 - 0.000346
N-hydroxy-N2-[(4-phenoxyphenyl)sulfonyl]-N2-(propan-2-yloxy)glycinamide
0.00026 - 0.000497
N2-(biphenyl-4-ylsulfonyl)-N-hydroxy-N2-(propan-2-yloxy)glycinamide
0.000007 - 0.000063
N2-(biphenyl-4-ylsulfonyl)-N-hydroxyglycinamide
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 7
-
-
7.4
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 8
-
-
5 - 9
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
30
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
expression is C/EBP-dependent
Manually annotated by BRENDA team
-
MMP-8 concentrations is significantly raised in abdominal aortic aneurysm compared with normal aorta
Manually annotated by BRENDA team
-
MMP-7 is upregulated in the infarcted tissue compared to healthy control areas
Manually annotated by BRENDA team
-
elevated MMP-8 is a marker of acute lung inflammation, and perhaps a contributor to acute lung injury, but is not necessarily an indicator of a poor outcome
Manually annotated by BRENDA team
-
MMP-8 is the major collagenase in human dentin
Manually annotated by BRENDA team
-
infection of human brain microvascular endothelial cells (HBMEC) with Neisseria meningitidis induces an increase in MMP-8 activity
Manually annotated by BRENDA team
-
MMP-8 is localized to mesenchymal cells within the adventitia of the aortic wall
Manually annotated by BRENDA team
-
of smokers and non-smokers, MMP-8 is increased in tissue from smokers, overview
Manually annotated by BRENDA team
-
MMP-8 is expressed in an inducible manner in both pro- and active forms on the surface of polymorphonuclear cell
Manually annotated by BRENDA team
-
induced by 4-nitroquinoline N-oxide
Manually annotated by BRENDA team
additional information
-
selective cell-dependent MMP secretion
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
binding of MMP-8 to the surface of polymorphonuclear cells promotes stability
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
53000
-
x * 53000, human, deglycosylated enzyme, SDS-PAGE, under reducing conditions, x * 64000-65000, human, SDS-PAGE, x * 85000, human, latent enzyme, SDS-PAGE, under reducing conditions
62000
-
human, PAGE
79000
-
x * 79000, recombinant mutant enzymes are purified in the proenzyme form and all display an apparent molecular mass of 79000 Da, SDS-PAGE
85000
-
x * 53000, human, deglycosylated enzyme, SDS-PAGE, under reducing conditions, x * 64000-65000, human, SDS-PAGE, x * 85000, human, latent enzyme, SDS-PAGE, under reducing conditions
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
molecular dynamic simulations of MMP-8 with and without bound inhibitor, the 144-155 loop of the enzyme undergoes a drastic decrease of mobility once complexed with both enantiomers, S1' subsite structure, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
-
proteolytic modification
-
recombinant mutant enzymes are purified in the proenzyme form and all display an apparent molecular mass of 79000 Da, 4-aminophenylmercuric acetate-initiated autolytic processing to the fully activated form of the purified mutants, generation of the 59000 Da active enzyme after removal of the propeptide
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure of the catalytic domain in non-covalent complex with the hydroxamate inhibitor BB-1909, space group P2(1)2(1)2(1), cell constants a : 4.47 nm, b : 8.08 nm, c : 10.81 nm
-
crystallized using hanging drop method, space group P2(1)2(1)2(1), cell dimesions a : 33.1 A, b : 68.9 A, c : 70.5 A
-
in complex with a primed and an unprimed-side inhibitor, hanging-drop vapor diffusion, space group P2(1)2(1)2(1), cell dimensions a : 32.98 A, b : 68.67 A, c : 70.49 A
-
in complex with inhibitor HONH-iBM-L-Ala-Gly-NH2, vapor-diffusion technique, hanging drop
-
MMP-8 in complex with inhibitors (S)- and (R)-alpha-arylsulfonylamino phosphonate, hanging drop vapor diffusion method at 18°C, mixing of 0.0015 ml of protein solution containing 6 mg/mL protein in 5 mM CaCl2, 100 mM NaCl, 0.5 mM ZnCl2, 3 mM MES-NaOH, 0.02% NaN3, pH 6.0, with 0.001 ml of inhibitor solution containing 1 mM inhibitor in 0.2 M MES-NaOH, 20% MeOH, pH 6.0, and 0.005 ml of PEG solution containing 10% m/v PEG 6000, 0.2 M MES-NaOH, 0.02% NaN3, pH 6.0, droplets are concentrated against a reservoir buffer containing 1.6 M sodium phosphate buffer, 0.02% NaN3, pH 6.0, X-ray diffraction structure determination and anaylsis at 1.56-1.94 A resolution
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
t1/2 for soluble MMP-8: 7.5 h, membrane-bound MMP-8 retains more than 80% of its activity after 18 h. Binding of MMP-8 to the surface of polymorphonuclear cells promotes stability
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
as latent enzyme
-
catalytic domain
-
from culture supernatant of phorbol myristate acetate stimulated neutrophils, immunoaffinity chromatography
-
whMMP-8 proenzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
catalytic domain heterologously expressed in Escherichia coli
-
MMP-8 and TIMP1 genotyping in head and neck squamous cell carcinoma, overview. The MMP8 genotype does not correlate with survival or MMP-8 level
-
recombinant catalytic domains displaying either Phe 79, PheMMP-8 or Met80, MetMMP-8
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
MMP-7 is upregulated after stroke in brain in the infarcted tissue compared to healthy control areas, overview
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
N188G
-
25% decrease in collagen cleavage, 30% decrease in cleavage of (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-[3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl]-Ala-Arg-NH2
N190L
-
unstable
Y189F
-
88% of wild-type activity with (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-[3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl]-Ala-Arg-NH2. Activity against type I collagen dripps 3fold compared with wild-type enzyme
additional information
-
genotyping and identification of the MMP8 single nucleotide polymorphism rs11225395, located 0.8 kB 5' of the transcription start site
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biotechnology
-
human MMP-8 is coupled to epoxy activated silica matrix in an immobilized enzyme reactor which is used for the online screening of known MMP-8 inhibitors in zonal chromatography and inhibition experiments
medicine