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Information on EC 3.4.24.63 - meprin B and Organism(s) Homo sapiens and UniProt Accession Q16820
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3.4.24.63 meprin BSpecify your search results
Word Map
- 3.4.24.63
- alzheimer
-
amyloid
- abeta
- gamma-secretase
- beta-amyloid
- plaque
- amyloid-beta
-
beta-site
-
amyloidogenic
- alpha-secretase
-
aspartyl
- cerebral
-
presenilins
-
senile
- neurodegenerative
- bace-1
-
swedish
-
sappalpha
-
neuropathology
- tau
-
neurotoxic
-
app-cleaving
- neuroblastoma
- beta-peptide
- ectodomains
- dementia
-
protein-cleaving
- medicine
-
nicastrin
- drug development
-
amyloidogenesis
-
tangles
-
isostere
-
memapsin
-
peptidomimetic
- abeta1-40
-
appswe
-
ad-like
-
hydroxyethylene
-
neurofibrillary
- adam10
- beta-protein
-
ad-associated
-
endoproteolytic
-
insulin-degrading
-
non-amyloidogenic
-
betaapp
- neprilysin
- pharmacology
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Hydrolysis of proteins, including azocasein, and peptides. Hydrolysis of -His5-/-Leu-, -Leu6-/-Cys-, -Ala14-/-Leu- and -Cys19-/-Gly- bonds in insulin B chain
Synonyms
beta-secretase, meprin b, metalloprotease meprin, meprinbeta, meprin-beta, cell surface sheddase, mouse meprin beta, metalloproteinase meprin beta, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
meprin beta
-
Meprin b
Meprin b
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
150679-52-0
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(7-methoxycoumarin-4-yl)acetyl-YVADAPK-(K-epsilon-DNP)-NH2 + H2O
?
-
-
-
?
(7-methyloxycoumarin-4-yl)acetyl-EDEDED-(K-epsilon-2,4-dinitrophenyl) + H2O
?
-
-
-
?
(7-methyloxycoumarin-4-yl)acetyl-EDEDED-NH2-(2,4-dinitrophenyl) + H2O
?
-
-
-
?
Abz-VKMDAE-EDDnp + H2O
?
wild-type beta-site fluorogenic substrate sequence
-
-
?
Abz-VNLDAE-EDDnp + H2O
?
Swedish mutant beta-site fluorogenic substrate sequence
-
-
?
alpha-secretase + H2O
?
meprin beta-mediated activation of the alpha-secretase
-
-
?
amyloid precursor protein + H2O
amyloid beta peptides
meprin beta initially sheds amyloid precursor protein, releasing different amyloid beta species with several cleavage sites identical with or proximal to the known beta-secretase cleavage site
-
-
?
amyloid precursor protein + H2O
amyloid precursor protein N-terminal fragments + amyloid beta protein
amyloid precursor protein APP751 + H2O
amyloid precursor protein N-terminal fragments + amyloid beta protein
recombinant human substrate, coexpressed with the enzyme in HEK-293T cells, or exogenous soluble meprin beta incubated with APP751 stably overexpressing 7WD10 cells, is able to produce amyloid precursor fragment N-APP20
-
-
?
fibrillar procollagen type I + H2O
fibrillar collagen type I + fibrillar collagen type I propeptide
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III. Cleavage sites are at positions YYRA1218-/-1219DDAN and VRDR1227/-1228DLEV for the alpha1(I) chain, and additionally GGGY1108-/-1109DFGY for alpha2(I). For the N-terminal propeptide SYGY166-/-167DEKS (alpha1(I)) and AAQY81-/-82DGKG (alpha2(I)) are identified as meprin cleavage sites
-
-
?
fibrillar procollagen type III + H2O
fibrillar collagen type III + fibrillar collagen type I propeptide
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III
-
-
?
interleukin-1beta precursor + H2O
interleukin-1beta + interleukin-1beta propeptide
proteolytic cleavage to a biologically active form
-
-
?
interleukin-6 + H2O
?
recombinant human substrate expressed in eukaryotic B9 cell line, inactivation. Human meprin B cleaves 35% and 65% of human interleukin-6 of about 22 kDa to a smaller product of about 21 kDa within 30 min and 2 h, respectively
-
-
?
KKGYVADAP-7-amido-4-methylcoumarin + H2O
KKGYVA + DAP-7-amido-4-methylcoumarin
-
-
-
?
lymphoepithelial Kazal-type-related inhibitor + H2O
?
a serine protease inhibitor
-
-
?
amyloid precursor protein + H2O
?
-
APP Is Processed by meprin beta in Vivo
-
-
?
N-Benzoyl-Tyr 4-aminobenzoate + H2O
?
-
rat or human enzyme, cleaves arylamide bond
-
-
?
tenascin-C + H2O
?
-
specific processing by meprinbeta, cleavage mechanism, overview. Meprinbeta-digested human tenascin-C is not able to interfere with fibronectin-mediated cell spreading, confirming cleavage in the anti-adhesive domain. Meprinbeta processing of human tenascin-C neutralizes its inhibitory effect on fibronectin-mediated cell spreading
-
-
?
tenascin-C + H2O
tenascin-C peptide fragments
-
mapping of proteolytic fragments generated by meprinbeta from the chicken tenascin-C and the human recombinant 250 kDa TN-C variant. In chicken tenascin-C, meprinbeta processes all three major splicing variants by removal of 10 kDa N-terminal and 38 kDa C-terminal peptides, leaving a large central part of subunits intact. A similar cleavage pattern exists for large human tenascin-C variant where two N-terminal peptides of 10 and 15 kDa and two C-terminal fragments of 40 and 55 kDa are removed from the intact subunit. N-terminal sequencing reveals the exact amino acid positions of cleavage sites. In both chicken and human tenascin-C N-terminal cleavages occur just before and/or after the heptad repeats involved in subunit oligomerization. In the human protein, an additional cleavage site is identified in the alternative fibronectin type III repeat, and a unique cleavage by meprinbeta is located to the 7th constant fibronectin type III repeat in both chicken and human tenascin-C, cleavage at this site removes the C-terminal domain involved in its anti-adhesive activity
-
-
?
ADAM10 + H2O
?
i.e. a disintegrin and metalloproteinase 10, reombinant C-terminally Myc-tagged substrate, recombinant N-terminally Strep-tagged meprin beta cleaves the ADAM10 prodomain at amino acids Gln198/Glu199 and Glu199/Glu200
-
-
?
ADAM17 + H2O
?
i.e. a disintegrin and metalloproteinase 17, reombinant C-terminally Myc-tagged substrate
-
-
?
ADAM9 + H2O
?
i.e. a disintegrin and metalloproteinase 9, reombinant C-terminally Myc-tagged substrate, recombinant N-terminally Strep-tagged meprin beta cleaves the ADAM9 prodomain at amino acids Gly189/Asp190 and Glu191/Glu192
-
-
?
amyloid precursor protein + H2O
?
meprin beta cleaves amyloid precursor protein at the beta-secretase site, giving rise to amyloidogenic peptides
-
-
?
amyloid precursor protein + H2O
?
recombinant soluble human APP695, cleavage at the beta-secretase site
-
-
?
amyloid precursor protein + H2O
?
APP, cleavage mechanism by meprin beta, overview
-
-
?
amyloid precursor protein + H2O
?
APP, the precursor protein is cleaved by meprin beta in distinct ways, either at the beta-secretase site resulting in increased levels of amyloid beta (Abeta) peptides, or at the N-terminus releasing 11 kDa, and 20 kDa peptide fragments. The N-terminal 11 kDa and 20 kDa peptide fragments represent physiological cleavage products
-
-
?
amyloid precursor protein + H2O
?
APP, cleavage mechanism by meprin beta, overview. Generation of truncated Abeta2-x peptides
-
-
?
amyloid precursor protein + H2O
?
APP, the precursor protein is cleaved by meprin beta in distinct ways, either at the beta-secretase site resulting in increased levels of amyloid beta (Abeta) peptides, or at the N-terminus releasing 11 kDa, and 20 kDa peptide fragments
-
-
?
amyloid precursor protein + H2O
amyloid precursor protein N-terminal fragments + amyloid beta protein
meprin beta can also process amyloid precursor protein in a manner reminiscent of beta-secretase, identification of cleavage sites of meprin beta in the amyloid beta sequence of the wild-type and Swedish mutant of amyloid precursor protein at positions p1 and p2, thereby generating amyloid beta variants starting at the first or second amino acid residue, mass spectrometry analysis, overview
-
-
?
amyloid precursor protein + H2O
amyloid precursor protein N-terminal fragments + amyloid beta protein
catalytic properties and cleavage sites of meprin beta within different amyloid precursor protein peptides, overview
-
-
?
pro-collagen I + H2O
collagen I + collagen I propeptide
cleavage of the C-terminal pro-domain
-
-
?
additional information
?
-
meprin B may play an important role in activation of the proinflammatory cytokine in various pathophysiological conditions
-
-
?
additional information
?
-
sheddase mechanism of meprin beta, overview
-
-
?
additional information
?
-
meprin beta preferentially cleaves substrates with acidic amino acids in P1'-position
-
-
?
additional information
?
-
comparison of cleavage sites of BACE-1 (EC 3.4.23.46) and meprin beta on APP wild-type and APPswe isoform. The protective A673T mutation in amyloid precursor protein (APP) results in reduced Abeta levels in patients, also prevents from meprin beta cleavage at position p2. Alterations of the amino acid composition close to the beta-secretase cleavage site may inhibit meprin beta activity on the generation of N-terminal truncated Abeta peptides
-
-
?
additional information
?
-
-
comparison of cleavage sites of BACE-1 (EC 3.4.23.46) and meprin beta on APP wild-type and APPswe isoform. The protective A673T mutation in amyloid precursor protein (APP) results in reduced Abeta levels in patients, also prevents from meprin beta cleavage at position p2. Alterations of the amino acid composition close to the beta-secretase cleavage site may inhibit meprin beta activity on the generation of N-terminal truncated Abeta peptides
-
-
?
additional information
?
-
specific N-terminal processing of ADAM9, 10, and 17 by meprin beta and identification of cleavage sites within their prodomains. Direct interaction of meprin beta and ADAM proteases. Meprin beta specifically cleaves ADAM9, 10, and 17 N-terminal of the furin cleavage site
-
-
?
additional information
?
-
the cleavage of a meprin beta substrate leads to generation of the prolyl tripeptidyl aminopeptidase (PtP, EC 3.4.14.12) substrate, and the activity of PtP results in release of a chromophore or fluorophore, coupled assay method evaluation, overview
-
-
?
additional information
?
-
-
whereas the expression of meprinbeta and tenascin-C does not overlap in normal colon tissue, inflamed lesions of the mucosa from patients with Crohn's disease exhibit many meprinbeta-positive leukocytes in regions where tenascin-C is strongly induced. At least under pathological conditions, meprinbeta might attack specific functional sites in tenascin-C that are important for its oligomerization and anti-adhesive activity
-
-
?
additional information
?
-
-
meprin interacts with epithelial Na+ channel (ENaC)
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
alpha-secretase + H2O
?
meprin beta-mediated activation of the alpha-secretase
-
-
?
amyloid precursor protein + H2O
amyloid beta peptides
meprin beta initially sheds amyloid precursor protein, releasing different amyloid beta species with several cleavage sites identical with or proximal to the known beta-secretase cleavage site
-
-
?
amyloid precursor protein + H2O
amyloid precursor protein N-terminal fragments + amyloid beta protein
meprin beta can also process amyloid precursor protein in a manner reminiscent of beta-secretase, identification of cleavage sites of meprin beta in the amyloid beta sequence of the wild-type and Swedish mutant of amyloid precursor protein at positions p1 and p2, thereby generating amyloid beta variants starting at the first or second amino acid residue, mass spectrometry analysis, overview
-
-
?
fibrillar procollagen type I + H2O
fibrillar collagen type I + fibrillar collagen type I propeptide
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III. Cleavage sites are at positions YYRA1218-/-1219DDAN and VRDR1227/-1228DLEV for the alpha1(I) chain, and additionally GGGY1108-/-1109DFGY for alpha2(I). For the N-terminal propeptide SYGY166-/-167DEKS (alpha1(I)) and AAQY81-/-82DGKG (alpha2(I)) are identified as meprin cleavage sites
-
-
?
fibrillar procollagen type III + H2O
fibrillar collagen type III + fibrillar collagen type I propeptide
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III
-
-
?
tenascin-C + H2O
?
-
specific processing by meprinbeta, cleavage mechanism, overview. Meprinbeta-digested human tenascin-C is not able to interfere with fibronectin-mediated cell spreading, confirming cleavage in the anti-adhesive domain. Meprinbeta processing of human tenascin-C neutralizes its inhibitory effect on fibronectin-mediated cell spreading
-
-
?
amyloid precursor protein + H2O
?
meprin beta cleaves amyloid precursor protein at the beta-secretase site, giving rise to amyloidogenic peptides
-
-
?
amyloid precursor protein + H2O
?
APP, cleavage mechanism by meprin beta, overview
-
-
?
amyloid precursor protein + H2O
?
APP, the precursor protein is cleaved by meprin beta in distinct ways, either at the beta-secretase site resulting in increased levels of amyloid beta (Abeta) peptides, or at the N-terminus releasing 11 kDa, and 20 kDa peptide fragments. The N-terminal 11 kDa and 20 kDa peptide fragments represent physiological cleavage products
-
-
?
additional information
?
-
meprin B may play an important role in activation of the proinflammatory cytokine in various pathophysiological conditions
-
-
?
additional information
?
-
meprin beta preferentially cleaves substrates with acidic amino acids in P1'-position
-
-
?
additional information
?
-
-
whereas the expression of meprinbeta and tenascin-C does not overlap in normal colon tissue, inflamed lesions of the mucosa from patients with Crohn's disease exhibit many meprinbeta-positive leukocytes in regions where tenascin-C is strongly induced. At least under pathological conditions, meprinbeta might attack specific functional sites in tenascin-C that are important for its oligomerization and anti-adhesive activity
-
-
?
additional information
?
-
-
meprin interacts with epithelial Na+ channel (ENaC)
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Zn2+
Zn2+
Ca2+
physiologic calcium concentrations display a dual role by (1) directly inhibiting meprin beta activity and (2) supporting meprin beta folding during biosynthesis
Zn2+
meprin beta is a metalloprotease of the astacin family characterized by a conserved zinc-binding motif (HExxHxxGFxHExxRxDR)
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-([(1,3-benzodioxol-5-ylsulfonyl)[2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
-
3-([(3-fluoro-4-methoxybenzyl)[2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
-
3-([(biphenyl-4-ylsulfonyl)[2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
-
3-([[(1R)-2-(hydroxyamino)-2-oxo-1-phenylethyl]amino]methyl)benzoic acid
-
3-([[(1S)-2-(hydroxyamino)-2-oxo-1-phenylethyl]amino]methyl)benzoic acid
-
3-([[(2R)-1-(hydroxyamino)-1-oxo-3-phenylpropan-2-yl]amino]methyl)benzoic acid
-
3-([[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]amino]methyl)benzoic acid
-
3-([[(2R)-3-carboxy-1-(hydroxyamino)-1-oxopropan-2-yl]amino]methyl)benzoic acid
-
3-([[(2R)-4-carboxy-1-(hydroxyamino)-1-oxobutan-2-yl]amino]methyl)benzoic acid
-
3-([[(2S)-1-(hydroxyamino)-1-oxo-3-phenylpropan-2-yl]amino]methyl)benzoic acid
-
3-([[(2S)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]amino]methyl)benzoic acid
-
3-([[(2S)-3-carboxy-1-(hydroxyamino)-1-oxopropan-2-yl]amino]methyl)benzoic acid
-
3-([[(2S)-4-carboxy-1-(hydroxyamino)-1-oxobutan-2-yl]amino]methyl)benzoic acid
-
3-([[(3-fluoro-4-methoxyphenyl)sulfonyl][2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
-
3-([[(4-carboxyphenyl)sulfonyl][2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
-
3-([[(4-fluorophenyl)sulfonyl][2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
-
3-([[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]methyl)benzenecarboperoxoic acid
-
3-([[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]methyl)benzoic acid
not only a potent inhibitor of meprin beta, but also a very potent inhibitor of MMP2, 9 and 13
3-[(3-carboperoxybenzyl)[2-(hydroxyamino)-2-oxoethyl]sulfamoyl]benzoic acid
-
3-[(3-carboxybenzyl)[2-(hydroxyamino)-2-oxoethyl]sulfamoyl]benzoic acid
-
3-[(E)-[4-formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]pyridin-2-yl]diazenyl]-7-nitronaphthalene-1,5-disulfonic acid
competitive inhibition, binding occurs in meprin beta active site
3-[([2-(hydroxyamino)-2-oxoethyl][[4-(trifluoromethoxy)phenyl]sulfonyl]amino)methyl]benzoic acid
-
3-[[(2,6-difluoro-4-methoxyphenyl)methyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic acid
-
3-[[(4-carboxyphenyl)methyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic acid
-
3-[[(4-chlorophenyl)methyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic acid
-
3-[[(4-cyanophenyl)methyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic acid
-
3-[[(4-fluorophenyl)methyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic acid
-
3-[[1,3-benzodioxol-5-ylmethyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic Acid
-
3-[[[2-(hydroxyamino)-2-oxo-ethyl]-[(4-biphenyl)methyl]amino]methyl]benzoic acid
-
3-[[[2-(hydroxyamino)-2-oxo-ethyl]-[(4-propoxyphenyl)methyl]amino]methyl]benzoic acid
-
3-[[[2-(hydroxyamino)-2-oxoethyl]-(p-tolylmethyl)amino]methyl]benzoic acid
-
3-[[[2-(hydroxyamino)-2-oxoethyl]-[(3-methoxyphenyl)methyl]amino]methyl]benzoic acid
-
3-[[[2-(hydroxyamino)-2-oxoethyl]-[(4-methoxyphenyl)methyl]-amino]methyl]benzoic acid
-
3-[[[3-(hydroxyamino)-3-oxopropyl]-[(4-methoxyphenyl)-methyl]amino]methyl]benzoic acid
-
3-[[[4-(hydroxyamino)-4-oxobutyl]-[(4-methoxyphenyl)methyl]amino]methyl]benzoic acid
-
4-([[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]methyl)benzoic acid
-
diethyl 3,3'-([[2-(hydroxyamino)-2-oxoethyl]imino]dimethanediyl)dibenzoate
-
N-hydroxy-N2-(4-methoxybenzyl)-N2-[(4-methoxyphenyl)sulfonyl]glycinamide
-
N-[1-[(1-amino-1-oxopropan-2-yl)amino]-3-(naphthalen-1-yl)-1-oxopropan-2-yl]-4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enamide
-
N-[2-(hydroxyamino)-2-oxoethyl]-N-[(4-methoxyphenyl)sulfonyl]-beta-alanine
-
N-[4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enoyl]-3-methylvalyl-N-(2-aminoethyl)-DL-alaninamide
-
N2-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-N-hydroxy-N2-[(4-methoxyphenyl)sulfonyl]glycinamide
-
N2-(bicyclo[2.2.1]hept-2-ylmethyl)-N-hydroxy-N2-[(4-methoxyphenyl)sulfonyl]glycinamide
-
N4-hydroxy-N1-[3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
-
NF 449
4,4',4'',4'''-[carbonyl- bis[imino-5,1,3-benzenetriyl-bis-(carbonylimino)]]tetrakis-(benzene-1,3-disulfonic acid)
[[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]acetic acid
-
3-[[(3-carboxyphenyl)sulfonyl-[2-(hydroxyamino)-2-oxo-ethyl]amino]methyl]benzoic acid
mixed type inhibition
3-[[(3-carboxyphenyl)sulfonyl-[2-(hydroxyamino)-2-oxo-ethyl]amino]methyl]benzoic acid
hyperbolic noncompetitive/mixed-type inhibition
3-[[[2-(hydroxyamino)-2-oxo-ethyl]-(4-methoxyphenyl)sulfonylamino]methyl]benzoic acid
mixed type inhibition
3-[[[2-(hydroxyamino)-2-oxo-ethyl]-(4-methoxyphenyl)sulfonylamino]methyl]benzoic acid
hyperbolic noncompetitive/mixed-type inhibition
actinonin
a hydroxamate derivate and naturally occurring compound produced in actinomycetes. Hydroxamate inhibitors chelate the zinc ion in the active site
Ca2+
calcium negatively regulates meprin beta activity and attenuates substrate cleavage
NF449
Nf449 is a suramin analogue, mixed competitive/noncompetitive inhibition, binding occurs in meprin beta active site
Pro-Leu-Gly-hydroxamate
binding structure in S subsites, overview. A decrease in solvent accessibility values at specific residues upon inhibitor binding occurs. The S subsite of the enzyme interacts with residues at P site of the inhibitor
additional information
binding sites and binding structure of hydroxamic acid derivative inhibitors, molecular dynamics simulation study, overview
-
additional information
alterations of the amino acid composition close to the beta-secretase cleavage site may inhibit meprin beta activity on the generation of N-terminal truncated Abeta peptides
-
additional information
-
alterations of the amino acid composition close to the beta-secretase cleavage site may inhibit meprin beta activity on the generation of N-terminal truncated Abeta peptides
-
additional information
analysis of binding sites of human meprins, screening of inhibitors by molecular dynamics simulation study, molecular docking, overview
-
additional information
structure-activity relationships of selective meprin beta inhibitors, synthesis and inhibitory potency, overview. Preference of meprin beta for acidic residues in the P1' position. Acidic modifications induce potent inhibition and over 100fold selectivity over other structurally related metalloproteases such as MMP-2 or ADAM10
-
additional information
structure-guided design, synthesis, and characterization of next-generation meprin beta inhibitors, overview. Molecular docking of compounds 6a, 8a, and 8i, to meprin beta using the crystal structure, PDB ID 4GWN, with manual replacement of Cd2+ by Zn2+. Cell viability assay is assessed in human hepatocellular carcinoma cell line Hep-G2 and in human neuroblastoma cell line SH-SY5Y
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
meprin beta is expressed as an inactive zymogen and requires proteolytic maturation by tryptic serine proteases, e.g. by matriptase-2 (MT2), but not by TMPRSS4 or pancreatic trypsin
-
additional information
the pro-enzyme is activated by proteoltyic cleavage of a propeptide
-
additional information
-
the pro-enzyme is activated by proteoltyic cleavage of a propeptide
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000007
(7-methoxycoumarin-4-yl)acetyl-YVADAPK-(K-epsilon-DNP)-NH2
pH 7.5, 25°C
0.074
KKGYVADAP-7-amido-4-methylcoumarin
pH 7.5, 30°C, recombinant enzyme
0.074
KKGYVADAP-7-amido-4-methylcoumarin
pH 7.4, 30°C, recombinant enzyme
additional information
additional information
enzyme kinetic data for meprin beta suggests hyperbolic v/S characteristics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000008
3-[(E)-[4-formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]pyridin-2-yl]diazenyl]-7-nitronaphthalene-1,5-disulfonic acid
pH 7.5, 25°C
0.00003
3-[[(3-carboxyphenyl)sulfonyl-[2-(hydroxyamino)-2-oxo-ethyl]amino]methyl]benzoic acid
0.00003
3-[[[2-(hydroxyamino)-2-oxo-ethyl]-(4-methoxyphenyl)sulfonylamino]methyl]benzoic acid
0.014
DL-Pro-DL-Leu-Gly-NH2
pH and temperature not specified in the publication
0.0089
galardin
pH and temperature not specified in the publication
0.0074
N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid
pH and temperature not specified in the publication
0.0074
N4-hydroxy-N1-[3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
pH and temperature not specified in the publication
0.014
Pro-Leu-Gly-hydroxamate
pH and temperature not specified in the publication
0.00003
3-[[(3-carboxyphenyl)sulfonyl-[2-(hydroxyamino)-2-oxo-ethyl]amino]methyl]benzoic acid
pH 7.5, 30°C, recombinant enzyme
0.00003
3-[[(3-carboxyphenyl)sulfonyl-[2-(hydroxyamino)-2-oxo-ethyl]amino]methyl]benzoic acid
pH 7.4, 30°C, recombinant enzyme
0.00003
3-[[[2-(hydroxyamino)-2-oxo-ethyl]-(4-methoxyphenyl)sulfonylamino]methyl]benzoic acid
pH 7.5, 30°C, recombinant enzyme
0.00003
3-[[[2-(hydroxyamino)-2-oxo-ethyl]-(4-methoxyphenyl)sulfonylamino]methyl]benzoic acid
pH 7.4, 30°C, recombinant enzyme
0.002
actinonin
pH and temperature not specified in the publication
additional information
additional information
inhibition kinetics, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0131
3,3'-([[2-(hydroxyamino)-2-oxoethyl]imino]dimethanediyl)dibenzamide
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000049
3,3'-([[2-(hydroxyamino)-2-oxoethyl]imino]dimethanediyl)dibenzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00027
3-([(1,3-benzodioxol-5-ylsulfonyl)[2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000375
3-([(3-fluoro-4-methoxybenzyl)[2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00108
3-([(biphenyl-4-ylsulfonyl)[2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.01165
3-([[(1R)-2-(hydroxyamino)-2-oxo-1-phenylethyl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.01215
3-([[(1S)-2-(hydroxyamino)-2-oxo-1-phenylethyl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00291
3-([[(2R)-1-(hydroxyamino)-1-oxo-3-phenylpropan-2-yl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00426
3-([[(2R)-1-(hydroxyamino)-1-oxopropan-2-yl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.01185
3-([[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000548
3-([[(2R)-3-carboxy-1-(hydroxyamino)-1-oxopropan-2-yl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000768
3-([[(2R)-4-carboxy-1-(hydroxyamino)-1-oxobutan-2-yl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.0155
3-([[(2S)-1-(hydroxyamino)-1-oxo-3-phenylpropan-2-yl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.0042
3-([[(2S)-1-(hydroxyamino)-1-oxopropan-2-yl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.0158
3-([[(2S)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.001325
3-([[(2S)-3-carboxy-1-(hydroxyamino)-1-oxopropan-2-yl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000654
3-([[(2S)-4-carboxy-1-(hydroxyamino)-1-oxobutan-2-yl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00065
3-([[(3-fluoro-4-methoxyphenyl)sulfonyl][2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00032
3-([[(4-carboxyphenyl)sulfonyl][2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00106
3-([[(4-fluorophenyl)sulfonyl][2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000377
3-([[2-(hydroxyamino)-2-oxoethyl]amino]methyl)benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00006
3-([[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]methyl)benzenecarboperoxoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00006
3-([[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]methyl)benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00006
3-[(3-carboperoxybenzyl)[2-(hydroxyamino)-2-oxoethyl]sulfamoyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00006
3-[(3-carboxybenzyl)[2-(hydroxyamino)-2-oxoethyl]sulfamoyl]benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00008
3-[(E)-[4-formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]pyridin-2-yl]diazenyl]-7-nitronaphthalene-1,5-disulfonic acid
Homo sapiens
pH 7.5, 25°C
0.0007
3-[([2-(hydroxyamino)-2-oxoethyl][[4-(trifluoromethoxy)phenyl]sulfonyl]amino)methyl]benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000347
3-[[(2,6-difluoro-4-methoxyphenyl)methyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000207
3-[[(4-carboxyphenyl)methyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000076
3-[[(4-chlorophenyl)methyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00032
3-[[(4-cyanophenyl)methyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000177
3-[[(4-fluorophenyl)methyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000285
3-[[1,3-benzodioxol-5-ylmethyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic Acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00031
3-[[2-(hydroxyamino)-2-oxoethyl]sulfamoyl]benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00022
3-[[3-(hydroxyamino)-3-oxopropyl]sulfamoyl]benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.001285
3-[[benzyl-[2-(hydroxyamino)-2-oxoethyl]amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00128
3-[[[2-(hydroxyamino)-2-oxo-ethyl]-[(4-biphenyl)methyl]amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00225
3-[[[2-(hydroxyamino)-2-oxo-ethyl]-[(4-propoxyphenyl)methyl]amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000386
3-[[[2-(hydroxyamino)-2-oxoethyl]-(p-tolylmethyl)amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000559
3-[[[2-(hydroxyamino)-2-oxoethyl]-[(3-methoxyphenyl)methyl]amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000077
3-[[[2-(hydroxyamino)-2-oxoethyl]-[(4-methoxyphenyl)methyl]-amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000643
3-[[[3-(hydroxyamino)-3-oxopropyl]-[(4-methoxyphenyl)-methyl]amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000742
3-[[[4-(hydroxyamino)-4-oxobutyl]-[(4-methoxyphenyl)methyl]amino]methyl]benzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000524
4,4'-([[2-(hydroxyamino)-2-oxoethyl]imino]dimethanediyl)dibenzoic acid
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00098
4-([[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]methyl)benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00041
4-[[2-(hydroxyamino)-2-oxoethyl]sulfamoyl]benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.09485
diethyl 3,3'-([[2-(hydroxyamino)-2-oxoethyl]imino]dimethanediyl)dibenzoate
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.03495
N-hydroxy-N2-(4-methoxybenzyl)-N2-[(4-methoxyphenyl)sulfonyl]glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.0257
N-hydroxy-N2-[(2-methoxy-4-methylphenyl)sulfonyl]glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.01885
N-hydroxy-N2-[(3-methoxyphenyl)sulfonyl]glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.00442
N-hydroxy-N2-[(4'-methoxybiphenyl-4-yl)sulfonyl]glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.0429
N-hydroxy-N2-[(4-methoxyphenyl)sulfonyl]-N2-(2-phenylethyl)glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.0388
N-hydroxy-N2-[(4-methoxyphenyl)sulfonyl]-N2-(3-methylbutyl)glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.03253
N-hydroxy-N2-[(4-methoxyphenyl)sulfonyl]-N2-methylglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.00902
N-hydroxy-N2-[(4-methoxyphenyl)sulfonyl]glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.0188
N-hydroxy-N2-[(4-phenoxyphenyl)sulfonyl]glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.4
N-[1-[(1-amino-1-oxopropan-2-yl)amino]-3-(naphthalen-1-yl)-1-oxopropan-2-yl]-4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enamide
Homo sapiens
pH and temperature not specified in the publication
0.00255
N-[2-(hydroxyamino)-2-oxoethyl]-N-[(4-methoxyphenyl)sulfonyl]-beta-alanine
Homo sapiens
pH and temperature not specified in the publication
0.2
N-[4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enoyl]-3-methylvalyl-N-(2-aminoethyl)-DL-alaninamide
Homo sapiens
pH and temperature not specified in the publication
0.00654
N2,N2-bis(1,3-benzodioxol-5-ylmethyl)-N-hydroxyglycinamide
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000023
N2,N2-bis(2,4-difluoro-3-hydroxybenzyl)-N-hydroxyglycinamide
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.0182
N2,N2-bis(2,4-difluoro-3-methoxybenzyl)-N-hydroxyglycinamide
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000552
N2,N2-bis(2,6-difluoro-3-hydroxybenzyl)-N-hydroxyglycinamide
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00291
N2,N2-bis(2-fluoro-3-hydroxybenzyl)-N-hydroxyglycinamide
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000272
N2,N2-bis(3,5-difluoro-4-hydroxybenzyl)-N-hydroxyglycinamide
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.012
N2,N2-bis(3-cyanobenzyl)-N-hydroxyglycinamide
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.000024
N2,N2-bis(4-chloro-2-fluoro-3-hydroxybenzyl)-N-hydroxyglycinamide
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.0128
N2,N2-bis(4-chloro-2-fluoro-3-methoxybenzyl)-N-hydroxyglycinamide
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00106
N2,N2-bis(4-fluoro-3-hydroxybenzyl)-N-hydroxyglycinamide
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.05695
N2,N2-bis[3-(difluoromethoxy)benzyl]-N-hydroxyglycinamide
Homo sapiens
40 mM Tris, pH 8.0, 30°C, recombinant enzyme
0.00193
N2-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-N-hydroxy-N2-[(4-methoxyphenyl)sulfonyl]glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.00742
N2-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-N-hydroxyglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.04387
N2-(bicyclo[2.2.1]hept-2-ylmethyl)-N-hydroxy-N2-[(4-methoxyphenyl)sulfonyl]glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.00385
N2-(biphenyl-4-ylsulfonyl)-N-hydroxyglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.04047
N2-benzyl-N-hydroxy-N2-[(4-methoxyphenyl)sulfonyl]glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.0375
N2-butyl-N-hydroxy-N2-[(4-methoxyphenyl)sulfonyl]glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.0312
N2-ethyl-N-hydroxy-N2-[(4-methoxyphenyl)sulfonyl]glycinamide
Homo sapiens
pH and temperature not specified in the publication
0.01477
N2-[(2,4-dimethylphenyl)sulfonyl]-N-hydroxyglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.0269
N2-[(3,4-dimethoxyphenyl)sulfonyl]-N-hydroxyglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.00043
N2-[(3,5-dichloro-4-hydroxyphenyl)sulfonyl]-N-hydroxyglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.00619
N2-[(3-fluoro-4-methoxyphenyl)sulfonyl]-N-hydroxyglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.00565
N2-[(4'-chlorobiphenyl-4-yl)sulfonyl]-N-hydroxyglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.00731
N2-[(4'-fluorobiphenyl-4-yl)sulfonyl]-N-hydroxyglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.01717
N2-[(4-chlorophenyl)sulfonyl]-N-hydroxyglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.01432
N2-[(4-fluorophenyl)sulfonyl]-N-hydroxyglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.01797
N2-[(5-chloro-2-methylphenyl)sulfonyl]-N-hydroxyglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.01026
N2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl]-N-hydroxyglycinamide
Homo sapiens
pH and temperature not specified in the publication
0.0004
N3-[(3-chloro-4-hydroxyphenyl)sulfonyl]-N-hydroxy-b-alaninamide
Homo sapiens
pH and temperature not specified in the publication
0.00598
[[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]acetic acid
Homo sapiens
pH and temperature not specified in the publication
0.00034
(4-[[2-(hydroxyamino)-2-oxoethyl]sulfamoyl]phenyl)acetic acid
Homo sapiens
pH and temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
whereas the expression of meprinbeta and tenascin-C does not overlap in normal colon tissue, inflamed lesions of the mucosa from patients with Crohn's disease exhibit many meprinbeta-positive leukocytes in regions where tenascin-C is strongly induced
additional information
meprin beta mRNA levels are increased in brains of Alzheimer's disease patients compared with age-matched control individuals
meprin beta localizes in regions of the lung with immature collagen. In human idiopathic pulmonary fibrosis (IPF) lungs meprin beta is mostly localized in epithelium
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
meprin beta is a secreted homodimeric multidomain type-I membrane metallopeptidase
-
meprin beta is expressed as a dimeric type 1 transmembrane protein
meprin beta is a membrane-bound protein with a transmembrane helix and a small C-terminal cytosolic domain
meprin beta is a secreted homodimeric multidomain type-I membrane metallopeptidase
additional information
meprin beta can be shed from the cell surface by a disintegrin and metalloprotease 10 and 17 (ADAM10/17), the soluble meprin beta is no longer capable of cleaving amyloid precursor protein at the beta-site
-
additional information
meprin beta homodimers are essentially membrane bound but may also be shed from the surface by ADAM-10 and -17
-
additional information
meprin beta is a type 1 transmembrane protein, but can be released from the cell surface by ectodomain shedding
-
additional information
meprin beta is primarily membrane-bound and forms asymmetric disulfide linked homodimer at the cell surface
-
additional information
meprin beta localisation changes upon bleomycin treatment
-
additional information
the extracellular metalloprotease meprin beta is expressed as a homodimer and is primarily membrane bound. Meprin beta can be released from the cell surface by its known sheddases ADAM10 and ADAM17. Shedding of meprin beta mutant G32R mediated by ADAM17 is impaired
-
additional information
-
meprin beta does not contain an additional inserted domain (I-domain)
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
evolution
-
meprin beta belongs to the astacin family of zinc-endopeptidases and the metzincin superfamily, characterized by the conserved motif HExxHxxGxxHxxxRxDR. Meprin beta is the only membrane-bound member of the astacin family
physiological function
additional information
evolution
meprin beta belongs to the astacin family within the metzincins, with a tight 1,4-beta-type Met turn located below the catalytic zinc site, featuring a strictly conserved methionine, M209
evolution
meprin beta is a metalloprotease of the astacin family characterized by a conserved zinc-binding motif (HExxHxxGFxHExxRxDR). Human meprin-alpha, EC 3.4.24.18, and -beta protease subunits are 55% identical at the amino acid level, while the substrate and peptide bond specificities vary markedly
evolution
meprin metalloproteases belong to the astacin family of zinc endopeptidases and the metzincin superfamily. Meprins belong to the astacin family of metalloproteases, comprising only six members in humans. These enzymes are characterized by a conserved zinc-binding motif (HExxHxxGxxHxxxRxDR) and by a sequence in close proximity to the active-site cleft, the so called Met-turn, that includes a tyrosine residue as a fifth zinc ligand. Within the astacin family, meprins exhibit a unique domain composition
evolution
human meprin beta ia a single-zinc metalloendoprotease of the astacin family
evolution
meprin beta belongs to the astacins of the metzincin superfamily
evolution
the astacin proteases meprin alpha and meprin beta are zinc-dependent metalloproteases of the metzincin superfamily
malfunction
enzyme downregulation causes impaired intestinal mucin release and barrier function, and decreases tensile strength in the skin, but it also leads to protection against sepsis and renal injury. Enzyme upregulation can cause fibrosis, pulmonary hypertension, the Kawasaki syndrome, inflammatory bowel disease, and is involved in nephritis, cancer, and Alzheimer's disease, overview
malfunction
ablation of one of the two zinc metalloproteinases, meprin beta and BMP-1, leads to different collagen I associated phenotypes in vivo
malfunction
the change to an arginine residue at position 32 represents an additional activation site used by furin-like proteases in the Golgi, which consequently leads to reduced shedding by ADAM17. The meprin beta G32R variant assesses cell proliferation, invasion through a collagen IV matrix, and outgrowth from tumor spheroids. Increased meprin beta G32R activity at the cell surface reduces cell proliferation, but increases cell invasion. The G32R meprin beta variant shows increased activity
malfunction
the protective A673T mutation in amyloid precursor protein (APP) results in reduced Abeta levels in patients, also prevents from meprin beta cleavage at position p2. Alterations of the amino acid composition close to the beta-secretase cleavage site may inhibit meprin beta activity on the generation of N-terminal truncated Abeta peptides
metabolism
calcium negatively regulates meprin beta activity and attenuates substrate cleavage
metabolism
meprins show higher substrate and cleavage specificity compared to matrix metalloproteases
metabolism
identification of a proteolytic pathway of meprin beta with ADAM proteases to control protease activities at the cell surface as part of the protease web
metabolism
important beta-site cleaving enzyme 1 (BACE-1)-independent contribution of the metalloprotease meprin beta within the amyloidogenic pathway. The anti-amyloidogenic alpha-secretase a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a direct competitor for APP at the cell surface, but also a sheddase of inactive pro-meprin beta. The activity of meprin beta is strictly extracellularly regulated within the protease web. Meprin beta itself is identified as an inducer of ADAM10 activity
metabolism
metalloprotease meprin beta is activated by transmembrane serine protease matriptase-2 at the cell surface thereby enhancing amyloid precursor protein (APP) shedding
metabolism
the zinc metalloproteinases meprin beta and BMP-1 are differentially regulated by CaCl2, overview
physiological function
meprin beta acts as a sheddase at the cell surface where it releases the entire ectodomain of amyloid precursor protein, this cleavage event at the so-called beta-site enables gamma-secretase to further cleave the remaining C-terminal fragment of APP within the membrane, thereby releasing amyloid beta-peptides, which are known to be involved in the onset and progression of Alzheimer's disease. The enzyme is involved in inflammation by the release and maturation of cytokines and proteoglycans, it induces extracellular matrix assembly and fibrosis, and enhances cancer progression through transactivation of epidermal growth factor receptors. The cleavage of fibrillar procollagen by the enzyme is required and sufficient to induce collagen fibril assembly
physiological function
meprin beta metalloproteinase is an important enzyme in extracellular matrix turnover, inflammation, and neurodegeneration in humans
physiological function
meprin-beta regulates production of pro-inflammatory factors via a disintegrin and metalloproteinase-10 (ADAM-10) dependent pathway in macrophages. Meprin-beta increases the production of pro-inflammatory cytokines, including interleukin-1beta, interleukin-18 and interleukin-6 in macrophages, but shows no effects on the level of ligands of epidermal growth factor receptor and its activation. Activation of NF-kappaB by meprin-beta is mediated by inhibiting ADAM10-downstream extracellular signal regulated kinase (ERK1/2) pathway, molecular mechanism, overview. Meprin-beta significantly induces the phosphorylation of ERK1/2 and its upstream MEK1/2
physiological function
processing of the amyloid precursor protein is of critical importance, the enzyme cleaves amyloid precursor protein and liberates soluble N-terminal amyloid precursor protein fragments
physiological function
procollagen III is processed to its mature form by meprin alpha and meprin beta, an essential step in collagen fibril assembly. The metalloprotease meprin beta is involved in inflammation, neurodegeneration, cancer and fibrosis, overview. The enzyme mediates intestinal leucocyte infiltration, in accordance with its ability to cleave adhesion molecules and components of the extracellular matrix. Meprin beta induces cell death in terminally differentiated keratinocytes. Increased meprin activity at the basement membrane leads to degradation of the renal tubular laminin-nidogen complex and other components of the basement membrane, and to the cleavage of cell-adhesion molecules (E-cadherin and tenascin-C), consequently injuring the tubular basement membrane and leading to leucocyte infiltration
physiological function
sheddase function of human meprin beta metalloproteinase at the plasma membrane, structural basis, overview. Ectodomain shedding at the cell surface is a major mechanism to regulate the extracellular and circulatory concentration or the activities of signaling proteins at the plasma membrane. Meprin beta sheds membrane-bound cytokines and growth factors, thereby contributing to inflammatory diseases, angiogenesis, and tumor progression
physiological function
a reduction in activity is reported under increasing calcium concentrations for meprin beta
physiological function
meprin beta contributes to collagen deposition in lung fibrosis and can also facilitate collagen maturation. They have been shown to cleave cell-cell contact molecules on epithelial cells such as E-cadherin and occludin. Meprin beta is positively regulated by TGF-beta1 in epithelial cells. Meprins are important for epithelial monolayer integrity, but meprins do not influence number and composition of inflammatory cells in the bleomycin treated lungs
physiological function
meprin beta is a membrane-bound metalloprotease involved in extracellular matrix assembly and inflammatory processes in health and disease. A disintegrin and metalloproteinase (ADAM)10 and ADAM17 are physiologically relevant sheddases of inactive promeprin beta, which influences its substrate repertoire and subsequent biologic functions. Specific N-terminal processing of ADAM9, 10, and 17 by meprin beta. Because ADAM prodomains can act as specific inhibitors, meprin beta plays a role in the regulation of ADAM activities. Prodomain cleavage by meprin beta causes increased ADAM protease activities, e.g. demonstrated by increased ectodomain shedding activity. As demonstrated by a bacterial activator of meprin beta and additional measurement of TNF-alpha shedding on bone marrow-derived macrophages, meprin beta/ADAM protease interactions likely influence inflammatory conditions. Meprin beta stimulates ADAM17 activity in macrophages because ADAM17-mediated TNF-alpha shedding is diminished in the absence of meprin beta
physiological function
meprin beta is potentially involved in disorders such as fibrosis and Alzheimer's disease
physiological function
neurotoxic amyloid-beta (Abeta) plaques are one of the pathological hallmarks in Alzheimer disease patient brains. Abeta accumulates in the brain upon sequential, proteolytic processing of the amyloid precursor protein (APP) by beta- and gamma-secretases. The metalloproteinase meprin beta acts as an alternative beta-secretase, besides BACE-1, capable of generating truncated Abeta2-x peptides. Regulation of the alternative beta-secretase meprin beta by ADAM-mediated shedding. In the small intestine, meprin beta is essential for the detachment of the mucus by cleaving mucine 2 (MUC2). This is crucial for the functionality of the mucus barrier to impede bacterial overgrowth and infection. Meprin beta is an alternative beta-secretase within the complex protease web, regulating APP processing in health and disease, overview. Shed meprin beta does not act as sheddase
physiological function
protease meprin beta is expressed as an inactive zymogen and requires proteolytic maturation by tryptic serine proteases. Maturation of full-length meprin beta is required for its activity as a cell surface sheddase, releasing the ectodomains of transmembrane proteins, e.g. amyloid precursor protein (APP)
physiological function
the precursor protein APP is cleaved by meprin beta in distinct ways, either at the beta-secretase site resulting in increased levels of amyloid beta (Abeta) peptides, or at the N-terminus releasing 11 kDa, and 20 kDa peptide fragments. The latter event is discussed to be rather neuroprotective, whereas the ectodomain shedding of APP by meprin beta reminiscent to BACE-1 is in line with the amyloid hypothesis of Alzheimer's disease, promoting neurodegeneration. The N-terminal 11 kDa and 20 kDa peptide fragments represent physiological cleavage products, since they are found in human brains under different diseased or non-diseased states, whereas the fragments are completely missing in brains of meprin bata knock-out animals. Meprin beta generates N-APP fragments that have neither negative nor positive influence on neuronal cell viability
physiological function
-
meprins stimulate epithelial Na+ channel (ENaC) expressed exogenously in Xenopus oocytes and endogenously in epithelial cells. Co-expression of ENaC subunits and meprin beta or alpha/beta in Xenopus oocytes increases amiloride-sensitive Na+ currents 2fold. The meprin-mediated increase in ENaC currents in oocytes and epithelial cell monolayers requires meprin beta, but not the alpha subunit
physiological function
-
meprin beta acts at the cell surface as a sheddase, cleaving transmembrane proteins, such as the amyloid precursor protein (APP). Meprins cleave compounds of the extracellular matrix such as laminin-V, collagen IV, fibronectin or nidogen 1, but also growth factors, cytokines and peptide hormones, including bradykinin, angiotensins, and gastrin
additional information
homology modeling of the protease domain of meprin beta on the astacin crystal structure and molecular dynamics simulation study, overview
additional information
meprin beta homodimers are essentially membrane bound but may also be shed fromthe surface byADAM-10 and -17. Multidomain structure, zymogenic determinants, catalytic domain, and MAM and TRAF domains in promeprin beta, and structure-activity analysis, homology modeling, overview
additional information
transcriptional regulation of meprin beta expression by the heterodimeric transcription factor AP-1 (activator protein 1), overview
additional information
enzyme sequence analysis and homology modeling of ADAM proteases, overview
additional information
human meprin beta is modelled using the template structure of astacin
additional information
meprin beta activity and localization is strictly regulated
additional information
-
meprin beta activity and localization is strictly regulated
additional information
molecular structure modelling of promeprin beta nd meprin beta, overview
additional information
structural differences between meprin beta and BMP-1 (EC 3.4.24.21). Molecular dynamics simulation
additional information
the extracellular metalloprotease meprin beta is expressed as a homodimer and is primarily membrane bound. Meprin beta can be released from the cell surface by its known sheddases ADAM10 and ADAM17. Activation of pro-meprin beta at the cell surface prevents its shedding, thereby stabilizing its proteolytic activity at the plasma membrane
additional information
the S1 and S2' subpockets within the active site of meprin beta are formed by arginines Arg184 and Arg146, respectively
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MEP1B_HUMAN
701
1
79571
Swiss-Prot
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
meprin beta is a multidomain metalloprotease and a dimeric type 1 transmembrane protein, enzyme domain structure, overview. The enzyme consists of a propeptide (PRO), a catalytic domain (CAT), a MAM (meprin A5 protein tyrosine phosphatase mu) domain, a TRAF (tumor-necrosis-factor-receptor-associated factor) domain, an EGF (epidermal growth factor) like domain, a transmembrane region and a C-terminal part
homodimer
dimer
-
the mature protease forms dimers which are stabilized by an intermolecular disulfide bond between the MAM domains
additional information
the enzyme assembles into either disulfide-linked homodimers or heterodimers with the closely related meprin alpha-subunit, EC 3.4.24.18. Meprin beta domain structure, detailed overview
homodimer
homodimer linked by a disulfide bridge, domain structure of human meprins, overview
homodimer
meprin beta is a homodimeric multidomain type-I membrane metallopeptidase
homodimer
domain composition and dimeric structure of the metalloprotease meprin beta, overview. The enzyme consists of propeptide, catalytic domain, meprin A5 protein tyrosine phosphatase micro domain, tumour-necrosis-factor-receptor-associated factor domain, epidermal growth factor-like domain, transmembrane region, and C-terminal part
homodimer
the enzyme consists of the protease domain with a 39 amino acid long inhibitory pro-peptide, a MAM domain, a TRAF domain, an EGF-like domain, a transmembrane helix, and a small C-terminal cytosolic domain
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
proteolytic modification
-
activation of meprin beta by proteolytic cleavage. Meprin beta contains a conserved sequence motif, which gives rise to enzymatic activation by tryptic serine proteases. Pancreatic trypsin performs this activation in the gut. Meprin beta cannot be activated by plasmin in the gut. In skin, the human tissue kallikrein-related peptidase 4 (KLK4), KLK5, and KLK8, cleave off the propeptide of meprin beta
glycoprotein
deglycosylation of recombinant enzyme by peptide-N-glycosidase
glycoprotein
the recombinant enzyme expressed in Pichia pastoris is N-glycosylated. Deglycosylation by endoglycosidase H does not alter the kinetics of the enzyme significantly
proteolytic modification
meprins are secreted as zymogens and are activated by trypsin-like serine proteases (e.g., human kallikrein related peptidases, KLK)
proteolytic modification
the recombinant N-terminally His-tagged human meprin beta zymogen is activated by cleavage with trypsin
proteolytic modification
zymogen promeprin beta is activated to mature meprin beta by proteolysis of the N-terminal prodomain, which is catalyzed by trypsin in the intestinal lumen and kallikrein-related peptidases (KLK-4, -5, and -8) in other tissues, overview
proteolytic modification
matriptase-2 (MT-2), a type 2 transmembrane protein, fully activates meprin beta at the cell surface
proteolytic modification
metalloprotease meprin beta is activated by transmembrane serine protease matriptase-2 (MT2) at the cell surface. No processing by TMPRSS4 or pancreatic trypsin. The cleavage site for maturation within the propeptide of meprin beta is in close proximity to the plasma membrane, crystal structure analysis, PDB ID 4GWM. Proteomic identification of the MT2-dependent cleavage in pro-meprin beta by mass spectrometry
proteolytic modification
pro-meprin beta is activated by trypsin (15:1 w/w) at room temperature in the presence of 10 mM CaCl2 for 10 min. Subsequently, trypsin is inactivated by the addition of 5 mM 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF)
proteolytic modification
proteolytic activation and shedding of meprin beta are mutually exclusive events. Cleavage of the pro-peptide completely blocks shedding of meprin beta by ADAM10 and ADAM17. The anti-amyloidogenic alpha-secretase a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a direct competitor for APP at the cell surface, but also a sheddase of inactive pro-meprin beta. Shedding of meprin beta by ADAM10/17 is completely abolished upon its activation by matrilysin-2 (MT-2, 3.4.24.23) at the cell surface. Only the proform of meprin beta can be shed. Meprin beta requires activation by tryptic proteases
proteolytic modification
proteolytic activation of pro-meprin beta at the cell surface, serine protease matriptase-2 (MT-2) is a membrane-bound activator of meprin beta. Shedding of meprin beta is mediated by endogenous ADAM10 or ADAM17. Shedding of meprin beta mutant G32R mediated by ADAM17 is impaired
proteolytic modification
the crystal structure of the zymogen form of meprin beta revealsthat the active side is shielded by the pro-peptide. Gln62 is directed away from the salt bridge that is formed by Glu163 and Lys248. The new N-terminus is formed by Asp62 after removal of the pro-peptide by tryptic serine protease cleavage between Arg61 and Gln62. In active meprin beta N62 forms a salt bridge with E163 and thus removes the new N-terminus from the active site, overview
proteolytic modification
the recombinant His6-tagged enzyme is activated by cleavage through trypsin
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure analysis of the ectodomain of dimeric human meprin beta, PDB codes 4GWN and 4GWM
zymogen promeprin beta and the major fragment of the meprin beta-ectoprotein, X-ray diffraction structure determination and analysis, modeling
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D240A
site-directed mutagenesis, the D204A mutant shows almost no signal at the cell surface, but strongly colocalized with the endoplasmic reticulum marker, low cell surface activity of D204A enzyme
D47A
the mutation is localized in the pro-peptide of the protease, the mutant is transported to the cell surface and exhibit expression comparable with wild-type meprin beta
G32R
naturally occuring mutant, the mutation is localized in the pro-peptide of the protease and identified in endometrium cancer, the mutant is transported to the cell surface and exhibit expression comparable with wild-type meprin beta, the mutant is more active against a peptide substrate (meprin beta-specific peptide substrate that is linked to a fluorogenic group (MCA) at the N-terminus and a quencher (DPN) at the C-terminus) and the interleukin-6 receptor than wild-type meprin beta. The change to an arginine residue at position 32 represents an additional activation site used by furin-like proteases in the Golgi, which consequently leads to reduced shedding by ADAM17. The meprin beta G32R variant assesses cell proliferation, invasion through a collagen IV matrix, and outgrowth from tumor spheroids. Increased meprin beta G32R activity at the cell surface reduces cell proliferation, but increases cell invasion. The G32R meprin beta variant shows increased activity. Phenotype, overview
G32R/R61S
site-directed mutagenesis, the double mutant has two altered sites that can no longer be proteolytically cleaved and cannot be activated or shedded
additional information
the expression patterns and cellular localizations of the two amino acid exchange variants do not differ from that of wild-type meprin beta
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant Flag-tagged meprin beta from HEK-293 cells by protein G affinity chromatography. Co-immunoprecipitation of C-terminal Flag-tagged meprin beta and C-terminal Myc-tagged ADAM proteases is performed in HEK-293T cells
recombinant His-tagged enzyme from Spodoptera frugiperda Sf9 insect cells by affinity chromatography
recombinant His6-tagged enzyme from Pichia pastoris strain X33 or SMD1168H by nickel affinity chromatography, enzyme activation by trypsin, and hydrophobic interaction chromatography, followed by gel filtration
recombinant N-terminally His-tagged human meprin beta zymogen from Hi5 insect cells by nickel affinity chromatography
recombinant N-terminally His-tagged meprin beta from HEK-293 cells by nickel affinity chromatography
recombinant N-terminally His6-tagged meprin beta from Pichia pastoris strain X33 by nickel affinity chromatography, activation of the enzyme by trypsin, followed by hydrophobic interaction chromatography, and gel filtration
recombinant soluble tail switch mutant pro-meprinbeta from BT1-TN-5B1-4 insect cells by nickel affinity chromatography after activation to meprinbeta by trypsin, trypsin is removed by chicken ovomucoid affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of mepbetaDELTATM, meprin beta coding region lacking the transmembrane and intracellular domains with V5 and hexahistidine C-terminal tags (termed as mepbetaDELTATM) in HEK-293F cells
gene MEP1B
gene MEP1B, recombinant expression of C-terminally or N-terminally His6-tagged enzyme in Pichia pastoris strain X33 or SMD1168H. The N-terminal signal sequence is replaced by the alpha-leader of Saccharomyces, enabling efficient secretion of the mature enzyme, harboring either an N-terminal or C-terminal His-tag. The recombinant enzyme is N-glycosylated and secreted as a dimer
gene MEP1B, recombinant expression of meprin beta in Pichia pastoris strain X-33
gene Mep1B, recombinant expression of N-terminally His-tagged meprin beta in HEK-293 cells, recombinant expression of meprin beta in COS-7 cells and coexpression with matrilysin-2 or pancreatic trypsin
gene MEP1B, recombinant expression of N-terminally His6-tagged meprin beta Pichia pastoris strain X33
gene MEP1B, recombinant expression of wild-type and mutant enzymes in HEK-293 cells
recombinant expression of C-terminally Flag-tagged meprin beta in HEK-293 cells
recombinant expression of FLAG-tagged enzyme mutants in HEK-293 and COS-7 cells, recombinant expression of N-terminally His-tagged human meprin beta zymogen in Hi5 insect cells via viral transfection method
recombinant expression of His-tagged enzyme in Spodoptera frugiperda Sf9 insect cells
transient co-expression of amyloid precursor protein APP751 and meprin beta in HEK293T cells. Generation of BACE1/2-KO mouse fibroblasts overexpressing human APP695 isoform and human meprin beta
expression of the soluble tail switch mutant pro-meprinbeta in BT1-TN-5B1-4 insect cells using the baculovirus transfection system
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in the ileal mucosa of Crohn's disease patients, mRNA levels of meprin beta are decreased
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
the astacin protease meprin beta is an emerging drug target for treatment of disorders such as kidney failure, fibrosis or inflammatory bowel disease
pharmacology
pharmacology
meprin-beta is strong candidate for a proinflammatory target
pharmacology
regulation of meprin activity by specific inhibition to reduce collagen maturation might be a suitable approach for the treatment of certain pathological conditions
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wolz, R.L.; Bond, J.S.
Meprins A and B
Methods Enzymol.
248
325-345
1995
Homo sapiens, Mus musculus, Rattus norvegicus
Herzog, C.; Kaushal, G.P.; Haun, R.S.
Generation of biologically active interleukin-1beta by meprin B
Cytokine
31
394-403
2005
Homo sapiens (Q16820)
Ambort, D.; Brellier, F.; Becker-Pauly, C.; Stoecker, W.; Andrejevic-Blant, S.; Chiquet, M.; Sterchi, E.E.
Specific processing of tenascin-C by the metalloprotease meprinbeta neutralizes its inhibition of cell spreading
Matrix Biol.
29
31-42
2010
Homo sapiens
Garca-Caballero, A.; Ishmael, S.; Dang, Y.; Gillie, D.; Bond, J.; Milgram, S.; Stutts, M.
Activation of the epithelial sodium channel by the metalloprotease meprin beta subunit
Channels
5
14-22
2011
Homo sapiens
Jefferson, T.; Causevic, M.; auf dem Keller, U.; Schilling, O.; Isbert, S.; Geyer, R.; Maier, W.; Tschickardt, S.; Jumpertz, T.; Weggen, S.; Bond, J.S.; Overall, C.M.; Pietrzik, C.U.; Becker-Pauly, C.
Metalloprotease meprin beta generates nontoxic N-terminal amyloid precursor protein fragments in vivo
J. Biol. Chem.
286
27741-27750
2011
Homo sapiens, Mus musculus
Broder, C.; Becker-Pauly, C.
The metalloproteases meprin alpha and meprin beta: Unique enzymes in inflammation, neurodegeneration, cancer and fibrosis
Biochem. J.
450
253-264
2013
Danio rerio, Homo sapiens (Q16820), Mus musculus (Q61847)
Madoux, F.; Tredup, C.; Spicer, T.P.; Scampavia, L.; Chase, P.S.; Hodder, P.S.; Fields, G.B.; Becker-Pauly, C.; Minond, D.
Development of high throughput screening assays and pilot screen for inhibitors of metalloproteases meprin alpha and beta
Biopolymers
102
396-406
2014
Homo sapiens (Q16820)
Arnold, P.; Schmidt, F.; Prox, J.; Zunke, F.; Pietrzik, C.; Lucius, R.; Becker-Pauly, C.
Calcium negatively regulates meprin beta activity and attenuates substrate cleavage
FASEB J.
29
3549-3557
2015
Homo sapiens (Q16820)
Li, Y.; Fan, Y.; Tang, J.; Li, J.; Yu, C.
Meprin-beta regulates production of pro-inflammatory factors via a disintegrin and metalloproteinase-10 (ADAM-10) dependent pathway in macrophages
Int. Immunopharmacol.
18
77-84
2014
Homo sapiens (Q16820)
Bien, J.; Jefferson, T.; Causevic, M.; Jumpertz, T.; Munter, L.; Multhaup, G.; Weggen, S.; Becker-Pauly, C.; Pietrzik, C.
The metalloprotease meprin beta generates amino terminal-truncated amyloid beta peptide species
J. Biol. Chem.
287
33304-33313
2012
Homo sapiens (Q16820), Homo sapiens
Keiffer, T.R.; Bond, J.S.
Meprin metalloproteases inactivate interleukin 6
J. Biol. Chem.
289
7580-7588
2014
Homo sapiens (Q16820), Homo sapiens, Rattus norvegicus (P28826)
Chaudhuri, A.; Sarkar, I.; Chakraborty, S.
Comparative analysis of binding sites of human meprins with hydroxamic acid derivative by molecular dynamics simulation study
J. Biomol. Struct. Dyn.
32
1969-1978
2014
Homo sapiens (Q16820)
Prox, J.; Arnold, P.; Becker-Pauly, C.
Meprin alpha and meprin beta: procollagen proteinases in health and disease
Matrix Biol.
44-46
7-13
2015
Homo sapiens (Q16820), Mus musculus (Q61847)
Arolas, J.; Broder, C.; Jefferson, T.; Guevara, T.; Sterchi, E.; Bode, W.; Stoecker, W.; Becker-Pauly, C.; Gomis-Rueth, F.
Structural basis for the sheddase function of human meprin beta metalloproteinase at the plasma membrane
Proc. Natl. Acad. Sci. USA
109
16131-16136
2012
Homo sapiens (Q16820)
Schulze, A.; Wermann, M.; Demuth, H.U.; Yoshimoto, T.; Ramsbeck, D.; Schlenzig, D.; Schilling, S.
Continuous assays for meprin alpha and beta using prolyl tripeptidyl aminopeptidase (PtP) from Porphyromonas gingivalis
Anal. Biochem.
559
11-16
2018
Homo sapiens (Q16820)
Jaeckle, F.; Schmidt, F.; Wichert, R.; Arnold, P.; Prox, J.; Mangold, M.; Ohler, A.; Pietrzik, C.U.; Koudelka, T.; Tholey, A.; Guetschow, M.; Stirnberg, M.; Becker-Pauly, C.
Metalloprotease meprin beta is activated by transmembrane serine protease matriptase-2 at the cell surface thereby enhancing APP shedding
Biochem. J.
470
91-103
2015
Homo sapiens (Q16820)
Ramsbeck, D.; Hamann, A.; Schlenzig, D.; Schilling, S.; Buchholz, M.
First insight into structure-activity relationships of selective meprin beta inhibitors
Bioorg. Med. Chem. Lett.
27
2428-2431
2017
Homo sapiens (Q16820)
Schneppenheim, J.; Scharfenberg, F.; Lucius, R.; Becker-Pauly, C.; Arnold, P.
Meprin beta and BMP-1 are differentially regulated by CaCl2
Cell Calcium
65
8-13
2017
Homo sapiens (Q16820)
Scharfenberg, F.; Armbrust, F.; Marengo, L.; Pietrzik, C.; Becker-Pauly, C.
Regulation of the alternative beta-secretase meprin beta by ADAM-mediated shedding
Cell. Mol. Life Sci.
76
3193-3206
2019
Homo sapiens (Q16820), Homo sapiens, Mus musculus (Q61847)
Chaudhuri, A.; Bera, A.K.; Sarkar, I.; Chakraborty, S.
Insights from analysis of binding sites of human meprins screening of inhibitors by molecular dynamics simulation study
Comb. Chem. High Throughput Screen.
19
246-258
2016
Homo sapiens (Q16820)
Wichert, R.; Scharfenberg, F.; Colmorgen, C.; Koudelka, T.; Schwarz, J.; Wetzel, S.; Potempa, B.; Potempa, J.; Bartsch, J.W.; Sagi, I.; Tholey, A.; Saftig, P.; Rose-John, S.; Becker-Pauly, C.
Meprin beta induces activities of A disintegrin and metalloproteinases 9, 10, and 17 by specific prodomain cleavage
FASEB J.
33
11925-11940
2019
Homo sapiens (Q16820), Mus musculus (Q61847), Mus musculus C57/BL6N (Q61847)
Becker-Pauly, C.; Pietrzik, C.U.
The metalloprotease meprin beta is an alternative beta-secretase of APP
Front. Mol. Neurosci.
9
159
2016
Homo sapiens (Q16820), Homo sapiens
Schaeffler, H.; Li, W.; Helm, O.; Krueger, S.; Boeger, C.; Peters, F.; Roecken, C.; Sebens, S.; Lucius, R.; Becker-Pauly, C.; Arnold, P.
The cancer-associated meprin beta variant G32R provides an additional activation site and promotes cancer cell invasion
J. Cell Sci.
132
jes220665
2019
Homo sapiens (Q16820)
Ramsbeck, D.; Hamann, A.; Richter, G.; Schlenzig, D.; Geissler, S.; Nykiel, V.; Cynis, H.; Schilling, S.; Buchholz, M.
Structure-guided design, synthesis, and characterization of next-generation meprin beta inhibitors
J. Med. Chem.
61
4578-4592
2018
Homo sapiens (Q16820)
Becker-Pauly, C.; Rose-John, S.
Meprin and ADAM metalloproteases two sides of the same coin?
Matrix Metalloproteinase Biology (ed. Sagi I. and Gaffney J.P.)
2015
115-130
2015
Homo sapiens
-
Schlenzig, D.; Wermann, M.; Ramsbeck, D.; Moenke-Wedler, T.; Schilling, S.
Expression, purification and initial characterization of human meprin beta from Pichia pastoris
Protein Expr. Purif.
116
75-81
2015
Homo sapiens (Q16820)
EXTERNAL LINKS (specific for EC-Number 3.4.24.63)
Transporter Classification Database (TCDB): 8.A.77.2.1
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