Information on EC 3.4.24.34 - neutrophil collagenase

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The expected taxonomic range for this enzyme is: Euarchontoglires

EC NUMBER
COMMENTARY
3.4.24.34
-
RECOMMENDED NAME
GeneOntology No.
neutrophil collagenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
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
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
collagenase-2
-
-
collagenase-2
-
-
collagenase-2
Mus musculus C57BL/6J
-
-
-
collagenases-8
-
-
collagenases-8
Rattus norvegicus Sprague-Dawley
-
-
-
EC 3.4.24.7
-
-
formerly
-
human neutrophil collagenase
-
-
matrix metalloproteinase
-
-
Matrix metalloproteinase 8
-
-
-
-
Matrix metalloproteinase-8
-
-
-
-
Matrix metalloproteinase-8
-
-
Matrix metalloproteinase-8
-
-
metalloproteinase-8
-
-
MetMMP-8
-
-
MMP-7
-
-
MMP-8
-
-
-
-
MMP-8
Mus musculus C57BL/6J
-
-
-
MMP-8
Rattus norvegicus Sprague-Dawley
-
-
-
MMP8
-
-
neutrophil collagenase
-
-
neutrophil collagenase MMP-8
-
-
neutrophil interstitial collagenase
-
-
PheMMP-8
-
-
PMNL collagenase
-
-
-
-
PMNL-CL
-
-
-
-
polymorphonuclear leukocyte collagenase
-
-
whMMP-8
-
-
CAS REGISTRY NUMBER
COMMENTARY
9001-12-1
not distinguishable from EC 3.4.24.3 and EC 3.4.24.7 in Chemical Abstracts
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
C57BL/6J mice
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
C57BL/6J mice
-
-
Manually annotated by BRENDA team
Sprague-Dawley
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
MMP-8-/- mice with acute lung injury have greater increases in lung polymorphonuclear neutrophils (PMNs) and macrophage counts, measures of alveolar capillary barrier injury, lung elastance, and mortality than wild-type mice with acute lung injury
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
-
MMP-8 inactivates macrophage inflammatory protein-1alpha to reduce acute lung inflammation and injury in mice
physiological function
-
MMP-8 is involved in the proteolytic cleavage of the tight junction protein occludin, resulting in its disappearance from the cell periphery and cleavage to a lower-sized 50-kDa protein in infected human brain microvascular endothelial cells
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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-DIAMIONOPROPIONYL-Ala-Arg-NH2 + H2O
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly + 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
-
-
-
?
bovine collagen I + H2O
?
show the reaction diagram
-
-
-
?
Cartilage aggrecan + H2O
hydrolyzed cartilage aggrecan
show the reaction diagram
-
cleavage at Glu373-Ala374 "aggrecanase" site in intraglobular domain
-
-
cartilage aggrecan + H2O
?
show the reaction diagram
-
-
-
?
Collagen + H2O
?
show the reaction diagram
-
-
-
-
?
Collagen + H2O
?
show the reaction diagram
-
-
-
-
?
Collagen + H2O
?
show the reaction diagram
-
initiates degradation of native collagen
-
-
-
Collagen + H2O
?
show the reaction diagram
-
type I and type II
-
-
?
Collagen + H2O
?
show the reaction diagram
-
MMP-8 is the major collagenase in human dentin
-
-
?
Dnp-Pro-Gln-Gly-Ile-Ala-Gly-Gln-(D)-Arg + H2O
?
show the reaction diagram
-
-
-
-
-
epithelial cell-derived neutrophil activating peptide-78 + H2O
?
show the reaction diagram
-
i.e. ENA-78, or CXCL5, a cytokine
-
-
?
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
-
-
-
-
-
interleukin-8 + H2O
?
show the reaction diagram
-
-
-
-
?
LIX + H2O
?
show the reaction diagram
-
a murine ELR+ CXC chemokine, a murine ELR+ CXC chemokine, MMP-8 cleaves the 92-amino acid peptide LIX between Ser-Val at position 4-5 to generate a NH2-terminus at Val5 designated LIX (5-92), the binding site is located on the MMP-8 hemopexin C-domain
-
-
?
M-1855 + H2O
?
show the reaction diagram
-
-
-
?
macrophage inflammatory protein-1 (MIP-1) alpha + H2O
?
show the reaction diagram
-
membrane-bound MMP-8 is a more potent MIP-1alpha-degrading enzyme than soluble MMP-8
-
-
?
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
-
from human
-
-
-
Monomeric type I collagen + H2O
collagen type I fragment TCA + collagen type I fragment TCB
show the reaction diagram
-
from guinea pig, best substrate, unlike EC 3.4.24.7 this enzyme cleaves type III collagen more slowly than type I, catalyzes single cleavage in alpha-chain
-
-
-
Monomeric type II collagen + H2O
collagen type II fragment TCA + collagen type II 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
-
-
three-quarter and one-quarter length fragments
-
Monomeric type III collagen + H2O
collagen type III fragment TCA + collagen type III fragmentTCB
show the reaction diagram
-
-
-
-
-
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 I collagen + H2O
?
show the reaction diagram
-
-
-
-
?
Type I collagen + H2O
?
show the reaction diagram
-
mechanical strain preserves collagen fibrils in the presence of MMP-8
-
-
?
type III collagen + H2O
?
show the reaction diagram
-
-
-
-
?
type III collagen + H2O
?
show the reaction diagram
-
-
-
-
?
type III collagen + H2O
?
show the reaction diagram
-
mechanism of interaction and cleavage of human type III collagen by fibroblast MMP-8 using a panel of recombinant human type III collagens containing engineered sequences in the vicinity of the cleavage site around residue 1785, e.g. mutant FG-5015 I785P, overview
-
-
?
Monomeric type III collagen + H2O
collagen type III fragment TCA + collagen type III fragmentTCB
show the reaction diagram
-
unlike EC 3.4.24.7 this enzyme cleaves type III collagen more slowly than type I
three-quarter and one-quarter length fragments
-
additional information
?
-
-
no hydrolysis of monomeric type IV or V collagen
-
-
-
additional information
?
-
-
expression of MMP-8 is positively associated with improved survival of the patients suffering squamous cell carcinoma of the tongue and the tendency is particularly prominent in females, MMP-8 has a protective, probably estrogen-related, role in mobile tongue carcinoma, overview
-
-
-
additional information
?
-
-
lipopolysaccharide responsiveness and neutrophil chemotaxis in vivo require polymorphonuclear MMP-8 activity, overview
-
-
-
additional information
?
-
-
MMP-8 can degrade all the components of the extracellular matrix
-
-
-
additional information
?
-
-
MMP-8 is involved in abdominal aortic aneurysm rupture, overview
-
-
-
additional information
?
-
-
tobacco-related increase in MMP-8 levels may be involved in periodontal disease in tobacco smokers, MMP-8 is also involved in other tobacco-related inflammatory diseases such as vascular and pulmonary diseases
-
-
-
additional information
?
-
-
no activity with the murine ELR+ CXC chemokines KC, MIP-2, and DCIP-1
-
-
-
additional information
?
-
-
MP-8 is involved in the proteolytic cleavage of the tight junction protein occludin
-
-
-
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
Collagen + H2O
?
show the reaction diagram
-
-
-
-
?
Collagen + H2O
?
show the reaction diagram
-
initiates degradation of native collagen
-
-
-
Collagen + H2O
?
show the reaction diagram
-
MMP-8 is the major collagenase in human dentin
-
-
?
epithelial cell-derived neutrophil activating peptide-78 + H2O
?
show the reaction diagram
-
i.e. ENA-78, or CXCL5, a cytokine
-
-
?
estrogen receptor alpha + H2O
?
show the reaction diagram
-
-
-
-
?
estrogen receptor beta + H2O
?
show the reaction diagram
-
-
-
-
?
interleukin-8 + H2O
?
show the reaction diagram
-
-
-
-
?
LIX + H2O
?
show the reaction diagram
-
a murine ELR+ CXC chemokine
-
-
?
Type I collagen + H2O
?
show the reaction diagram
-
-
-
-
?
Type I collagen + H2O
?
show the reaction diagram
-
-
-
-
?
Type I collagen + H2O
?
show the reaction diagram
-
mechanical strain preserves collagen fibrils in the presence of MMP-8
-
-
?
type III collagen + H2O
?
show the reaction diagram
-
-
-
-
?
type III collagen + H2O
?
show the reaction diagram
-
-
-
-
?
macrophage inflammatory protein-1 (MIP-1) alpha + H2O
?
show the reaction diagram
-
membrane-bound MMP-8 is a more potent MIP-1alpha-degrading enzyme than soluble MMP-8
-
-
?
additional information
?
-
-
expression of MMP-8 is positively associated with improved survival of the patients suffering squamous cell carcinoma of the tongue and the tendency is particularly prominent in females, MMP-8 has a protective, probably estrogen-related, role in mobile tongue carcinoma, overview
-
-
-
additional information
?
-
-
lipopolysaccharide responsiveness and neutrophil chemotaxis in vivo require polymorphonuclear MMP-8 activity, overview
-
-
-
additional information
?
-
-
MMP-8 can degrade all the components of the extracellular matrix
-
-
-
additional information
?
-
-
MMP-8 is involved in abdominal aortic aneurysm rupture, overview
-
-
-
additional information
?
-
-
tobacco-related increase in MMP-8 levels may be involved in periodontal disease in tobacco smokers, MMP-8 is also involved in other tobacco-related inflammatory diseases such as vascular and pulmonary diseases
-
-
-
additional information
?
-
-
MP-8 is involved in the proteolytic cleavage of the tight junction protein occludin
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Zn2+
-
metalloproteinase, presumptive zinc-binding motif
Zn2+
-
present in the active site, involved in teh catalytic mechanism
Zn2+
-
zinc endoproteinase
Zn2+
-
Zn2+ metalloendopeptidase
Zn2+
-
zinc endopeptidase
Zn2+
-
a zinc metalloendoprotease
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
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
malonic acid hydroxamate
-
-
MMP-8 hemopexin C-domain
-
recombinantly expressed, in excess inhibits the processing of LIX cytokine by blocking the binding site, overview
-
MMP-8 inhibitor I
-
modulation of 5-fluorouracil pharmacokinetic by irradiation is reversed by MMP-8 inhibitor
-
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
-
-
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
-
MMP-8 inhibitor I
-
in the presence of specific MMP-8 I inhibitor formation of the occludin cleavage product is prevented
-
additional information
-
no inhibition by PMSF, pepstatin, N-ethylmaleimide, cystatin or E-64
-
additional information
-
resistant to inhibition by tissue inhibitor of metalloproteinase-1 and tissue inhibitor of metalloproteinase-2
-
additional information
-
inhibitor-induced conformational changes at the active site, structure-activity relationships, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
additional information
-
the enzyme expression is induced by estrogen
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0279
-
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly-norvaline-His-Ala-Arg-NH2
-
pH 7.0, 37C, 3-protonated substrate
0.0315
-
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly-norvaline-His-Ala-Arg-NH2
-
pH 7.0, 37C, 4-protonated substrate
0.0457
-
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly-norvaline-His-Ala-Arg-NH2
-
pH 7.0, 37C, unprotonated, 1-protonated and 2-protonated substrate
0.0622
-
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly-norvaline-His-Ala-Arg-NH2
-
pH 7.0, 37C, 5-protonated substrate
0.0184
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-DIAMIONOPROPIONYL-Ala-Arg-NH2
-
pH 7.0, 37C, 1-protonated and 2-protonated substrate
0.0208
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-DIAMIONOPROPIONYL-Ala-Arg-NH2
-
pH 7.0, 37C, unprotonated substrate
0.0265
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-DIAMIONOPROPIONYL-Ala-Arg-NH2
-
pH 7.0, 37C, 3-protonated substrate
0.046
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-DIAMIONOPROPIONYL-Ala-Arg-NH2
-
pH 7.0, 37C, 4-protonated and 5-protonated substrate
0.0194
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-L-diaminopropionyl-Ala-Arg-NH2
-
pH 5.0-8.0, 37C, 1-protonated substrate
0.028
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-L-diaminopropionyl-Ala-Arg-NH2
-
pH 5.0-8.0, 37C, 2-protonated substrate
0.0465
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-L-diaminopropionyl-Ala-Arg-NH2
-
pH 5.0-8.0, 37C, 3-protonated and 4-protonated substrate
0.000208
-
bovine collagen I
-
pH 7.0, 37C, 1-protonated substrate
0.0533
-
bovine collagen I
-
pH 7.4, 37C
0.102
-
bovine collagen I
-
pH 7.0, 37C, 4-protonated and 5-protonated substrate
0.128
-
bovine collagen I
-
pH 7.0, 37C, 2-protonated substrate
0.958
-
bovine collagen I
-
pH 7.0, 37C, unprotonated substrate
14.4
-
bovine collagen I
-
pH 7.0, 37C, 3-protonated substrate
0.0006
-
guinea pig collagen type I
-
37C
-
0.0007
-
human collagen type I
-
37C
-
0.0011
-
human collagen type II
-
37C
-
0.0018
-
human collagen type III
-
37C
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
180
-
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly-norvaline-His-Ala-Arg-NH2
-
pH 7.0, 37C, 5-protonated substrate
246
-
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly-norvaline-His-Ala-Arg-NH2
-
pH 7.0, 37C, unprotonated, 1-protonated and 2-protonated substrate
250
-
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly-norvaline-His-Ala-Arg-NH2
-
pH 7.0, 37C, 3-protonated substrate
570
-
(7-methoxycoumarin-4-yl)acetyl-Pro-cyclohexylalanine-Gly-norvaline-His-Ala-Arg-NH2
-
pH 7.0, 37C, 4-protonated substrate
145
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-diaminopropionyl-Ala-Arg-NH2
-
pH 5.0-8.0, 37C, 4-protonated substrate
164
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-diaminopropionyl-Ala-Arg-NH2
-
pH 5.0-8.0, 37C, unprotonated substrate
342
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-diaminopropionyl-Ala-Arg-NH2
-
pH 5.0-8.0, 37C, 2-protonated substrate
522
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-diaminopropionyl-Ala-Arg-NH2
-
pH 5.0-8.0, 37C, 3-protonated substrate
148
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-DIAMIONOPROPIONYL-Ala-Arg-NH2
-
pH 7.0, 37C, 5-protonated substrate
164
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-DIAMIONOPROPIONYL-Ala-Arg-NH2
-
pH 7.0, 37C, unprotonated, 1-protonated and 2-protonated substrate
324
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-DIAMIONOPROPIONYL-Ala-Arg-NH2
-
pH 7.0, 37C, 3-protonated substrate
562
-
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-DIAMIONOPROPIONYL-Ala-Arg-NH2
-
pH 7.0, 37C, 4-protonated substrate
0.0109
-
bovine collagen I
-
pH 7.0, 37C, 4-protonated and 5-protonated substrate
0.47
-
bovine collagen I
-
pH 7.0, 37C, unprotonated and 1-protonated substrate
4.75
-
bovine collagen I
-
pH 7.4, 37C
15
-
bovine collagen I
-
pH 7.0, 37C, 2-protonated substrate
1120
-
bovine collagen I
-
pH 7.0, 37C, 3-protonated substrate
0.00161
-
guinea pig collagen type I
-
37C
-
0.00178
-
human collagen type I
-
37C
-
0.00065
-
human collagen type II
-
37C
-
0.000233
-
human collagen type III
-
37C
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0081
-
(2R,S)-HONH-Mal(Me/Bn)-1,2,9,10-tetrahydroisoquinolide
-
pH 7.6, 25C
0.045
-
(2R,S)-HONH-Mal(Me/Bn)-alpha-naphthylamide
-
pH 7.6, 25C
0.0096
-
(2R,S)-HONH-Mal(Me/Bn)-NH-CH2CH2-Ph
-
pH 7.6, 25C
0.00024
-
(2R,S)-HONH-Mal(Me/Bn)-NH-CH2CH2CH2-Ph
-
pH 7.6, 25C
0.00038
-
(2R,S)-HONH-Mal(Me/Bn)-NH-CH2CH2CH2CH2-Ph
-
pH 7.6, 25C
0.0011
-
(2R,S)-HONH-Mal(Me/Bn)-NHBn
-
pH 7.6, 25C
0.041
-
(2R,S)-HONH-Mal(Me/Bn)-NHBn-(p-COOH)
-
pH 7.6, 25C
0.044
-
(2R,S)-HONH-Mal(Me/Bn)-NHPh
-
pH 7.6, 25C
0.011
-
(2R,S)-HONH-Mal(Me/Bn)-Oet
-
pH 7.6, 25C
0.041
-
(2R,S)-HONH-Mal(Me/i-Bu)-Oet
-
pH 7.6, 25C
0.0023
-
(2R,S)-HONH-Mal(NHAc/Bn)-NHBn
-
pH 7.6, 25C
0.0019
-
(2R,S)-HONH-Mal(OH/Bn)-NHBn
-
pH 7.6, 25C
0.0000007
-
(2S,3R)-2-methyl-3-(2-methylpropyl)-1-(N-hydroxy)-4-(O-methyl)-L-tyrosine-N-methylamide
-
pH 7.5, 37C, BB-16
0.000002
-
(N-1(R)-carboxyethyl)-alpha-(S)-(4-phenyl-3-butynyl)glycyl-L-O-methyltyrosine, N-methylamide
-
pH 7.5, 37C, SA751
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0000006
-
(1R)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate
-
pH 7.5, 25C
0.0007
-
(1S)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate
-
pH 7.5, 25C
0.000005
-
N-hydroxy-2-(2-[[4-(4-methoxyphenoxy)phenyl]sulfonyl]phenyl)acetamide
-
pH 7.5, 37, free MMP-8 FLU plates read
0.00001
-
N-hydroxy-2-(2-[[4-(4-methoxyphenoxy)phenyl]sulfonyl]phenyl)acetamide
-
pH 7.5, 37, free MMP-8 HPLC-FLU
0.000034
-
N-hydroxy-2-(2-[[4-(4-methoxyphenoxy)phenyl]sulfonyl]phenyl)acetamide
-
pH 7.5, 37, free MMP-8 HPLC-FLU
0.000065
-
N-hydroxy-N2-[(4'-methoxybiphenyl-4-yl)sulfonyl]-N2-(propan-2-yloxy)glycinamide
-
pH 7.5, 37, free MMP-8 FLU plates read
0.00023
-
N-hydroxy-N2-[(4'-methoxybiphenyl-4-yl)sulfonyl]-N2-(propan-2-yloxy)glycinamide
-
pH 7.5, 37, free MMP-8 HPLC-FLU
0.00033
-
N-hydroxy-N2-[(4'-methoxybiphenyl-4-yl)sulfonyl]-N2-(propan-2-yloxy)glycinamide
-
pH 7.5, 37, free MMP-8 HPLC-FLU
0.000065
-
N-hydroxy-N2-[(4-phenoxyphenyl)sulfonyl]-N2-(propan-2-yloxy)glycinamide
-
pH 7.5, 37, free MMP-8 FLU plates read
0.00025
-
N-hydroxy-N2-[(4-phenoxyphenyl)sulfonyl]-N2-(propan-2-yloxy)glycinamide
-
pH 7.5, 37, free MMP-8 HPLC-FLU
0.000346
-
N-hydroxy-N2-[(4-phenoxyphenyl)sulfonyl]-N2-(propan-2-yloxy)glycinamide
-
pH 7.5, 37, free MMP-8 HPLC-FLU
0.00026
-
N2-(biphenyl-4-ylsulfonyl)-N-hydroxy-N2-(propan-2-yloxy)glycinamide
-
pH 7.5, 37, free MMP-8 FLU plates read
0.000435
-
N2-(biphenyl-4-ylsulfonyl)-N-hydroxy-N2-(propan-2-yloxy)glycinamide
-
pH 7.5, 37, free MMP-8 HPLC-FLU
0.000497
-
N2-(biphenyl-4-ylsulfonyl)-N-hydroxy-N2-(propan-2-yloxy)glycinamide
-
pH 7.5, 37, free MMP-8 HPLC-FLU
0.000007
-
N2-(biphenyl-4-ylsulfonyl)-N-hydroxyglycinamide
-
pH 7.5, 37, free MMP-8 FLU plates read
0.00003
-
N2-(biphenyl-4-ylsulfonyl)-N-hydroxyglycinamide
-
pH 7.5, 37, free MMP-8 HPLC-FLU
0.000063
-
N2-(biphenyl-4-ylsulfonyl)-N-hydroxyglycinamide
-
pH 7.5, 37, free MMP-8 HPLC-FLU
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
0.13 mg fibrillar guinea pig collagen type I/mg enzyme/min, 0.09 mg human collagen type III/mg enzyme/min, 25C
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
assay at
7.4
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
assay at
30
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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-8 is localized to mesenchymal cells within the adventitia of the aortic wall
Manually annotated by BRENDA team
-
matrix metalloproteinase-8 is increased at the site of abdominal aortic aneurysm rupture
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
-
lipopolysacchride-treated
Manually annotated by BRENDA team
-
polymorphonuclear
Manually annotated by BRENDA team
-
expression of MMP-8 does not change significantly in ovariectomized rat
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
expression of MMP-8 does not change significantly in ovariectomized rat
-
Manually annotated by BRENDA team
-
of smokers and non-smokers, MMP-8 is increased in tissue from smokers, overview
Manually annotated by BRENDA team
-
concentration of circulating MMP-8 is increased in periodontal disease patients compared to healthy controls, overview. Treatment reduces the level by by 35%, 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
-
TIMP(tissue inhibitor of metalloproteinase)-resistant, active MMP-8 expressed on the surface of activated polymorphonuclear cells is likely to be an important form of MMP-8, regulating the lung inflammation and collagen turnover in vivo
Manually annotated by BRENDA team
-
MMP-8 levels are higher in serum from men with cardiovascular disease, e.g. artherosclerosis, and in smokers compared to healthy men, which is correlated with an altered MMP-8/TIMP-1 ratio, overview
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
induced by 4-nitroquinoline N-oxide
Manually annotated by BRENDA team
-
Achilles tendon, immunohistochemic analysis of MMP-8, overview
Manually annotated by BRENDA team
-
MMP-8 is localized to mesenchymal cells within the adventitia of the aortic wall
Manually annotated by BRENDA team
additional information
-
selective cell-dependent MMP secretion
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
binding of MMP-8 to the surface of polymorphonuclear cells promotes stability
Manually annotated by BRENDA team
-
circulating MMP-8
-
Manually annotated by BRENDA team
-
the enzyme is secreted
-
Manually annotated by BRENDA team
-
membrane-bound MMP-8 accounts for 92% of the matrix metalloproteinase-mediated polymorphonuclear cell surface type I collagenase activity
Manually annotated by BRENDA team
-
membrane-bound MMP-8 is a more potent MIP-1alpha-degrading enzyme than soluble MMP-8
Manually annotated by BRENDA team
-
membrane-bound MMP-8 is a more potent MIP-1alpha-degrading enzyme than soluble MMP-8
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
62000
-
-
human, PAGE
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
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
?
-
x * 79000, recombinant mutant enzymes are purified in the proenzyme form and all display an apparent molecular mass of 79000 Da, SDS-PAGE
?
-
x * 85000, Pro-MMP-8, x * 65000, active mature MMP-8
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 ACCESSION NO.
COMMENTARY
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
proteolytic modification
-
the pro-MMP-8 is processed to its active form
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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 18C, 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
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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 ACCESSION NO.
LITERATURE
as latent enzyme
-
catalytic domain
-
from culture supernatant of phorbol myristate acetate stimulated neutrophils, immunoaffinity chromatography
-
whMMP-8 proenzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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
-
MMP-8 expression anaylsis, overview
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
MMP-7 is upregulated after stroke in brain in the infarcted tissue compared to healthy control areas, overview
-
ibuprofen upregulates expressions of matrix metalloproteinase-8, as well as MMP-1, MMP-9, and MMP-13, without affecting expressions of types I and III collagen in tendon cells
-
the amount of plasma MMP-8 is increased by whole pelvic irradiation (2.8fold by 0.5 Gy and 5.3fold by 2 Gy) in comparison with controls
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
E198A
-
mutant enzyme is not activated by 4-aminophenylmercuric acetate, no collagen cleavage activity
additional information
-
genotyping and identification of the MMP8 single nucleotide polymorphism rs11225395, located 0.8 kB 5' of the transcription start site
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
-
construction of MMP-8 knockout mice by gene targeting, MMP-8-deficient female mice develop tongue squamous cell carcinoma at a significantly higher incidence than wild-type mice exposed to carcinogen 4-nitroquinoline-N-oxide, overview
additional information
-
MMP8-/- mice, of a mixed C57BL/6J/129 background, deficient in collagenase-2/MMP-8 are more susceptible to develop skin cancer compared to wild-type mice, mutant mice show a significant delay in wound closure and an altered inflammatory response in their wounds, with a delay of neutrophil infiltration during the first days and a persistent inflammation at later time points, alterations in the TGF-beta1 signaling pathway and by an apoptosis defect in MMP8-/- mice, phenotype, overview
additional information
-
polymorphonuclear cell infiltration towards lipopolysaccharides is abrogated in MMP-8-null mice
additional information
Mus musculus C57BL/6J
-
MMP8-/- mice, of a mixed C57BL/6J/129 background, deficient in collagenase-2/MMP-8 are more susceptible to develop skin cancer compared to wild-type mice, mutant mice show a significant delay in wound closure and an altered inflammatory response in their wounds, with a delay of neutrophil infiltration during the first days and a persistent inflammation at later time points, alterations in the TGF-beta1 signaling pathway and by an apoptosis defect in MMP8-/- mice, phenotype, overview
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
-
implicated in cancer, arthritis, joint destruction and Alzheimer's disease
medicine
-
design of anticancer or other drugs which should be highly selective for their particular MMP targets
medicine
-
elevated MMP-8 in bronchoalveolar lavage fluid 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