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

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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.24 Metalloendopeptidases
                3.4.24.34 neutrophil collagenase
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Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Cleavage of interstitial collagens in the triple helical domain. Unlike EC 3.4.24.7, interstitial collagenase, this enzyme cleaves type III collagen more slowly than type I
Synonyms
matrix metalloproteinase, mmp-8, matrix metalloproteinase-8, neutrophil collagenase, matrix metalloproteinase 8, human neutrophil collagenase, collagenase-2, metalloproteinase-8, pmnl-cl, polymorphonuclear leukocyte collagenase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
collagenase-2
-
-
human neutrophil collagenase
-
-
matrix metalloproteinase
-
-
Matrix metalloproteinase 8
-
-
-
-
Matrix metalloproteinase-8
metalloproteinase-8
-
-
MetMMP-8
-
-
MMP-7
-
-
MMP-8
MMP8
-
-
neutrophil collagenase
-
-
neutrophil collagenase MMP-8
-
-
neutrophil interstitial collagenase
-
-
PheMMP-8
-
-
PMNL collagenase
-
-
-
-
PMNL-CL
-
-
-
-
whMMP-8
-
-
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
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-diaminipropionyl-Ala-Arg-NH2 + H2O
?
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-DIAMIONOPROPIONYL-Ala-Arg-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-L-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
collagen type 1 + 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
-
-
-
-
?
guinea pig collagen type I + H2O
?
show the reaction diagram
-
-
-
-
?
human collagen type I + H2O
?
show the reaction diagram
-
-
-
-
?
human collagen type II + H2O
?
show the reaction diagram
-
-
-
-
?
human collagen type III + 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 SUBSTRATE
NATURAL PRODUCT
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
collagen type 1 + H2O
?
show the reaction diagram
in dentin
-
-
?
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
INHIBITOR
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
-
-
2-(arylsulfonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
-
2-(arylsulfonyl)-1,2,3,4-tetrahydroisoquinoline-3-hydroxamate
-
batimastat
-
BB-94, peptidomimetic MMP inhibitor
BB-1909
-
-
EDTA
-
-
GM6001
-
an MMP inhibitor
HONH-iBM-L-Ala-Gly-NH2
-
-
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
-
-
I-COL 043
-
-
Ile-Pro-Glu-Asn-Phe-Phe-Gly
-
aggrecan as substrate
isovitexin
interacts with enzyme residues Val112, Ser218, Leu119, Glu118, Asn226, Ser225, Thr224, Asn184, Phe192, and Asp115, binding structure analysis, and modelling, overview
malonic acid hydroxamate
-
-
MMP-8 inhibitor I
-
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
-
-
N-hydroxy-N2-[(4'-methoxybiphenyl-4-yl)sulfonyl]-N2-(propan-2-yloxy)glycinamide
-
-
N-hydroxy-N2-[(4-phenoxyphenyl)sulfonyl]-N2-(propan-2-yloxy)glycinamide
-
-
N-hydroxy-N2-[(4-phenoxyphenyl)sulfonyl]valinamide
-
-
N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid
NNGH
N2-(biphenyl-4-ylsulfonyl)-N-hydroxy-N2-(propan-2-yloxy)glycinamide
-
-
N2-(biphenyl-4-ylsulfonyl)-N-hydroxyglycinamide
-
-
RO200-1770
-
-
RO204-1924
-
-
RO206-0027
-
-
RO206-0032
-
-
Thr-Glu-Gly-Glu-Ala-Arg-Gly
-
aggrecan as substrate
TIMP-1
-
TIMP-1 from brain is upregulated in in the infarcted tissue compared to healthy control areas, overview
-
TIMP-2
-
highly produced in brain microvessels
-
tissue inhibitor of matrix metalloproteinase-1
-
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
-
Tissue inhibitor of metalloproteinase-I
-
i.e. TIMP-I
-
vitexin
interacts with enzyme residues Leu193, Tyr219, Ala161, Asn218, His207, Glu198, Gly158, Pro217, His201, and Val194, binding structure analysis, and modelling, overview
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
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-diaminipropionyl-Ala-Arg-NH2
-
pH 7.0, 37°C, 1-protonated and 2-protonated substrate
-
0.0265 - 0.046
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-diaminopropionyl-Ala-Arg-NH2
0.0208
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-DIAMIONOPROPIONYL-Ala-Arg-NH2
-
pH 7.0, 37°C, unprotonated substrate
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 - 562
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-diaminopropionyl-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
-
-
7.2
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 8
-
-
5 - 9
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
assay at room temperature
25
-
assay at
30
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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
-
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
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
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
additional information
MMP-8 differs from other MMPs in that it has an insertion that enlarges its active site
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
MMP8_HUMAN
467
0
53412
Swiss-Prot
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
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
SUBUNIT
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
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
-
crystal structures of MMP-8 have been solved, PDB IDs 3DNG, 3DPE, 1ZVX
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
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E198A
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
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
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
the recombinant fusion enzyme shows much greater retention of activity when stored refrigerated without glycerol
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
as latent enzyme
-
catalytic domain
from culture supernatant of phorbol myristate acetate stimulated neutrophils, immunoaffinity chromatography
-
recombinant His-tagged thioredoxin-S-fusion enzyme from Escherichia coli strain BL21 by nicke affinity chromatography, ultrafiltration, tag cleavage by thrombin, followed by gel filtration, recombinant His-/claMP-tagged enzyme is purified by nicel affinity chromatography, tag cleavage by factor Xa, and gel filtration. Reaction with Factor Xa leads to incomplete cleavage but the uncut fusion protein is easily removed by gel filtration
whMMP-8 proenzyme
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
catalytic domain heterologously expressed in Escherichia coli
-
gene MMP8, recombinant production of soluble, active, stable MMP-8 as His-tagged N-terminal thioredoxin-S-fusion protein in high yield in Escherichia coli strain BL21, method optimization and evaluation, construction and expression of recombinant enzyme with a metal binding claMP tag replacing the thioredoxin fusion
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
-
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
diagnostics
correlation of salivary levels of MMP-8 and periodontal parameters of chronic periodontitis establish MMP-8 as a noninvasive marker for the early diagnosis of chronic periodontitis
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hasty, K.A.; Jeffrey, J.J.; Hibbs, M.S.; Welgus, H.G.
The collagen substrate specificity of human neutrophil collagenase
J. Biol. Chem.
262
10048-10052
1987
Homo sapiens
Manually annotated by BRENDA team
Hasty, K.A.; Pourmotabbed, T.F.; Goldberg, G.I.; Thompson, J.P.; Spinella, D.G.; Stevens, R.M.; Mainardi, C.L.
Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases
J. Biol. Chem.
265
11421-11424
1990
Homo sapiens
Manually annotated by BRENDA team
Knuper, S.; Krmer, S.; Reinke, H.; Tschesche, H.
Characterization and activation of procollagenase from human polymorphonuclear leucocytes. N-terminal sequence determination of the proenzyme and various proteolytically activated forms
Eur. J. Biochem.
189
295-300
1990
Homo sapiens
Manually annotated by BRENDA team
Fosang, A.J.; Last, K.; Neame, P.J.; Murphy, G.; Knuper, S.; Tschesche, H.; Hughes, C.E.; Caterson, B.; Hardingham, T.E.
Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A374 in the interglobular domain of cartilage aggrecan
Biochem. J.
304
347-351
1994
Homo sapiens
Manually annotated by BRENDA team
Fasciglione, G.F.; Marini, S.; D'Alessio, S.; Politi, V.; Coletta, M.
pH- and temperature-dependence of functional modulation in metalloproteinases. A comparison between neutrophil collagenase and gelatinases A and B
Biophys. J.
79
2138-2149
2000
Homo sapiens
Manually annotated by BRENDA team
Betz, M.; Huxley, P.; Davies, S.J.; Mushtaq, Y.; Pieper, M.; Tschesche, H.; Bode, W.; Gomis-Ruth, F.X.
1.8-A crystal structure of the catalytic domain of human neutrophil collagenase (matrix metalloproteinase-8) complexed with a peptidomimetic hydroxamate primed-side inhibitor with a distinct selectivity profile
Eur. J. Biochem.
247
356-363
1997
Homo sapiens
Manually annotated by BRENDA team
Arner, E.C.; Decicco, C.P.; Cherney, R.; Tortorella, M.D.
Cleavage of native cartilage aggrecan by neutrophil collagenase (MMP-8) is distinct from endogenous cleavage by aggrecanase
J. Biol. Chem.
272
9294-9299
1997
Homo sapiens
Manually annotated by BRENDA team
Marini, S.; Fasciglione, G.F.; de Sanctis, G.; D'Alessio, S.; Politi, V.; Coletta, M.
Cleavage of bovine collagen I by neutrophil collagenase MMP-8. Effect of pH on the catalytic properties as compared to synthetic substrates
J. Biol. Chem.
275
18657-18663
2000
Homo sapiens
Manually annotated by BRENDA team
Brandstetter, H.; Grams, F.; Glitz, D.; Lang, A.; Huber, R.; Bode, W.; Krell, H.W.; Engh, R.A.
The 1.8-A crystal structure of a matrix metalloproteinase 8-barbiturate inhibitor complex reveals a previously unobserved mechanism for collagenase substrate recognition
J. Biol. Chem.
276
17405-17412
2001
Homo sapiens
Manually annotated by BRENDA team
Gioia, M.; Fasciglione, G.F.; Marini, S.; D'Alessio, S.; De Sanctis, G.; Diekmann, O.; Pieper, M.; Politi, V.; Tschesche, H.; Coletta, M.
Modulation of the catalytic activity of neutrophil collagenase MMP-8 on bovine collagen I. Role of the activation cleavage and of the hemopexin-like domain
J. Biol. Chem.
277
23123-23130
2002
Homo sapiens
Manually annotated by BRENDA team
Graf von Roedern, E.; Brandstetter, H.; Engh, R.A.; Bode, W.; Grams, F.; Moroder, L.
Bis-substituted malonic acid hydroxamate derivatives as inhibitors of human neutrophil collagenase (MMP8)
J. Med. Chem.
41
3041-3047
1998
Homo sapiens
Manually annotated by BRENDA team
Matter, H.; Schwab, W.; Barbier, D.; Billen, G.; Haase, B.; Neises, B.; Schudok, M.; Thorwart, W.; Schreuder, H.; Brachvogel, V.; Lonze, P.; Weithmann, K.U.
Quantitative structure-activity relationship of human neutrophil collagenase (MMP-8) inhibitors using comparative molecular field analysis and X-ray structure analysis
J. Med. Chem.
42
1908-1920
1999
Homo sapiens (P22894), Homo sapiens
Manually annotated by BRENDA team
Gavuzzo, E.; Pochetti, G.; Mazza, F.; Gallina, C.; Gorini, B.; D'Alessio, S.; Pieper, M.; Tschesche, H.; Tucker, P.A.
Two crystal structures of human neutrophil collagenase, one complexed with a primed- and the other with an unprimed-side inhibitor: implications for drug design
J. Med. Chem.
43
3377-3385
2000
Homo sapiens (P22894), Homo sapiens
Manually annotated by BRENDA team
Brandstetter, H.; Engh, R.A.; Von Roedern, E.G.; Moroder, L.; Huber, R.; Bode, W.; Grams, F.
Structure of malonic acid-based inhibitors bound to human neutrophil collagenase. A new binding mode explains apparently anomalous data
Protein Sci.
7
1303-1309
1998
Homo sapiens
Manually annotated by BRENDA team
Wilson, W.R.; Schwalbe, E.C.; Jones, J.L.; Bell, P.R.; Thompson, M.M.
Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm
Br. J. Surg.
92
828-833
2005
Homo sapiens
Manually annotated by BRENDA team
Khanna-Gupta, A.; Zibello, T.; Idone, V.; Sun, H.; Lekstrom-Himes, J.; Berliner, N.
Human neutrophil collagenase expression is C/EBP-dependent during myeloid development
Exp. Hematol.
33
42-52
2005
Homo sapiens
Manually annotated by BRENDA team
Fligiel, S.E.; Standiford, T.; Fligiel, H.M.; Tashkin, D.; Strieter, R.M.; Warner, R.L.; Johnson, K.J.; Varani, J.
Matrix metalloproteinases and matrix metalloproteinase inhibitors in acute lung injury
Hum. Pathol.
37
422-430
2006
Homo sapiens
Manually annotated by BRENDA team
Pelman, G.R.; Morrison, C.J.; Overall, C.M.
Pivotal molecular determinants of peptidic and collagen triple helicase activities reside in the S3 subsite of matrix metalloproteinase 8 (MMP-8): the role of hydrogen bonding potential of ASN188 and TYR189 and the connecting cis bond
J. Biol. Chem.
280
2370-2377
2005
Homo sapiens
Manually annotated by BRENDA team
Owen, C.A.; Hu, Z.; Lopez-Otin, C.; Shapiro, S.D.
Membrane-bound matrix metalloproteinase-8 on activated polymorphonuclear cells is a potent, tissue inhibitor of metalloproteinase-resistant collagenase and serpinase
J. Immunol.
172
7791-7803
2004
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Sulkala, M.; Tervahartiala, T.; Sorsa, T.; Larmas, M.; Salo, T.; Tjaederhane, L.
Matrix metalloproteinase-8 (MMP-8) is the major collagenase in human dentin
Arch. Oral Biol.
52
121-127
2007
Homo sapiens
Manually annotated by BRENDA team
Tuomainen, A.M.; Nyyssoenen, K.; Laukkanen, J.A.; Tervahartiala, T.; Tuomainen, T.P.; Salonen, J.T.; Sorsa, T.; Pussinen, P.J.
Serum matrix metalloproteinase-8 concentrations are associated with cardiovascular outcome in men
Arterioscler. Thromb. Vasc. Biol.
27
2722-2728
2007
Homo sapiens
Manually annotated by BRENDA team
Liu, K.Z.; Hynes, A.; Man, A.; Alsagheer, A.; Singer, D.L.; Scott, D.A.
Increased local matrix metalloproteinase-8 expression in the periodontal connective tissues of smokers with periodontal disease
Biochim. Biophys. Acta
1762
775-780
2006
Homo sapiens
Manually annotated by BRENDA team
Korpi, J.T.; Kervinen, V.; Maeklin, H.; Vaeaenaenen, A.; Lahtinen, M.; Laeaerae, E.; Ristimaeki, A.; Thomas, G.; Ylipalosaari, M.; Astroem, P.; Lopez-Otin, C.; Sorsa, T.; Kantola, S.; Pirilae, E.; Salo, T.
Collagenase-2 (matrix metalloproteinase-8) plays a protective role in tongue cancer
Br. J. Cancer
98
766-775
2008
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Wilson, W.R.; Anderton, M.; Schwalbe, E.C.; Jones, J.L.; Furness, P.N.; Bell, P.R.; Thompson, M.M.
Matrix metalloproteinase-8 and -9 are increased at the site of abdominal aortic aneurysm rupture
Circulation
113
438-445
2006
Homo sapiens
Manually annotated by BRENDA team
Pochetti, G.; Gavuzzo, E.; Campestre, C.; Agamennone, M.; Tortorella, P.; Consalvi, V.; Gallina, C.; Hiller, O.; Tschesche, H.; Tucker, P.A.; Mazza, F.
Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates
J. Med. Chem.
49
923-931
2006
Homo sapiens
Manually annotated by BRENDA team
Aschi, M.; Besker, N.; Re, N.; Pochetti, G.; Coletti, C.; Gallina, C.; Mazza, F.
Stereoselectivity by enantiomeric inhibitors of matrix metalloproteinase-8: new insights from molecular dynamics simulations
J. Med. Chem.
50
211-218
2007
Homo sapiens
Manually annotated by BRENDA team
Marcaccini, A.M.; Novaes, A.B.; Meschiari, C.A.; Souza, S.L.; Palioto, D.B.; Sorgi, C.A.; Faccioli, L.H.; Tanus-Santos, J.E.; Gerlach, R.F.
Circulating matrix metalloproteinase-8 (MMP-8) and MMP-9 are increased in chronic periodontal disease and decrease after non-surgical periodontal therapy
Clin. Chim. Acta
409
117-122
2009
Homo sapiens
Manually annotated by BRENDA team
Cuadrado, E.; Rosell, A.; Penalba, A.; Slevin, M.; Alvarez-Sabin, J.; Ortega-Aznar, A.; Montaner, J.
Vascular MMP-9/TIMP-2 and neuronal MMP-10 up-regulation in human brain after stroke: a combined laser microdissection and protein array study
J. Proteome Res.
8
3191-3197
2009
Homo sapiens
Manually annotated by BRENDA team
Williams, K.E.; Olsen, D.R.
Matrix metalloproteinase-1 cleavage site recognition and binding in full-length human type III collagen
Matrix Biol.
28
373-379
2009
Homo sapiens
Manually annotated by BRENDA team
Pradhan-Palikhe, P.; Vesterinen, T.; Tarkkanen, J.; Leivo, I.; Sorsa, T.; Salo, T.; Mattila, P.S.
Plasma level of tissue inhibitor of matrix metalloproteinase-1 but not that of matrix metalloproteinase-8 predicts survival in head and neck squamous cell cancer
Oral Oncol.
46
514-518
2010
Homo sapiens
Manually annotated by BRENDA team
Mazzini, F.; Nuti, E.; Petri, A.; Rossello, A.
Immobilization of matrix metalloproteinase 8 (MMP-8) for online drug screening
J. Chromatogr. B
879
756-762
2011
Homo sapiens
Manually annotated by BRENDA team
Flynn, B.; Bhole, A.; Saeidi, N.; Liles, M.; Dimarzio, C.; Ruberti, J.
Mechanical strain stabilizes reconstituted collagen fibrils against enzymatic degradation by mammalian collagenase matrix metalloproteinase 8 (MMP-8)
PLoS ONE
5
e12337
2010
Homo sapiens
Manually annotated by BRENDA team
Schubert-Unkmeir, A.; Konrad, C.; Slanina, H.; Czapek, F.; Hebling, S.; Frosch, M.
Neisseria meningitidis induces brain microvascular endothelial cell detachment from the matrix and cleavage of occludin: A role for MMP-8
PLoS Pathog.
6
1-15
2010
Homo sapiens
Manually annotated by BRENDA team
Fang, C.; Wen, G.; Zhang, L.; Lin, L.; Moore, A.; Wu, S.; Ye, S.; Xiao, Q.
An important role of matrix metalloproteinase-8 in angiogenesis in vitro and in vivo
Cardiovasc. Res.
99
146-155
2013
Mus musculus (O70138), Homo sapiens (P22894), Homo sapiens
Manually annotated by BRENDA team
Thirkettle, S.; Decock, J.; Arnold, H.; Pennington, C.; Jaworski, D.; Edwards, D.
Matrix metalloproteinase 8 (collagenase 2) induces the expression of interleukins 6 and 8 in breast cancer cells
J. Biol. Chem.
288
16282-16294
2013
Homo sapiens (P22894), Homo sapiens
Manually annotated by BRENDA team
Lee, E.; Han, J.; Woo, M.; Shin, J.; Park, E.; Kang, J.; Moon, P.; Baek, M.; Son, W.; Ko, Y.; Choi, J.; Kim, H.
Matrix metalloproteinase-8 plays a pivotal role in neuroinflammation by modulating TNF-alpha activation
J. Immunol.
193
2384-2393
2014
Mus musculus (O70138), Mus musculus, Homo sapiens (P22894)
Manually annotated by BRENDA team
Hedenbjoerk-Lager, A.; Hamberg, K.; Paeaekkoenen, V.; Tjaederhane, L.; Ericson, D.
Collagen degradation and preservation of MMP-8 activity in human dentine matrix after demineralization
Arch. Oral Biol.
68
66-72
2016
Homo sapiens (P22894), Homo sapiens
Manually annotated by BRENDA team
Gupta, N.; Gupta, N.; Gupta, A.; Khan, S.; Bansal, N.
Role of salivary matrix metalloproteinase-8 (MMP-8) in chronic periodontitis diagnosis
Front. Med.
9
72-76
2015
Homo sapiens (P22894), Homo sapiens
Manually annotated by BRENDA team
Abu Bakar, A.R.; Ripen, A.M.; Merican, A.F.; Mohamad, S.B.
Enzymatic inhibitory activity of Ficus deltoidea leaf extract on matrix metalloproteinase-2, 8 and 9
Nat. Prod. Res.
33
1765-1768
2019
Homo sapiens (P22894)
Manually annotated by BRENDA team
McNiff, M.L.; Haynes, E.P.; Dixit, N.; Gao, F.P.; Laurence, J.S.
Thioredoxin fusion construct enables high-yield production of soluble, active matrix metalloproteinase-8 (MMP-8) in Escherichia coli
Protein Expr. Purif.
122
64-71
2016
Homo sapiens (P22894)
Manually annotated by BRENDA team