Information on EC 3.4.24.B6 - matrix metalloproteinase-20

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The expected taxonomic range for this enzyme is: Tetrapoda

EC NUMBER
COMMENTARY hide
3.4.24.B6
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
matrix metalloproteinase-20
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
proteolytic cleavage of ameloblastin
show the reaction diagram
proteolytic degradation of ameloblastin
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
185766-51-2
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
fragment; Caiman crocodilus apaporiensis
UniProt
Manually annotated by BRENDA team
C57Bl6 mice
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
fragment
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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Mmp20-deficient mouse ameloblasts can initiate, terminate, and reinitiate the secretory stage of enamel development
metabolism
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TGF-beta signaling involved in amelogenesis is partially mediated by regulating the expression of MMP20 mRNA
physiological function
additional information
-
genetic defects in MMP20 are involved in the hypomaturation-type enamel defect
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
aggrecan + H2O
?
show the reaction diagram
cleavage site is Asn341-Phe342
-
?
ameloblastin + H2O
?
show the reaction diagram
ameloblastin + H2O
ameloblastin fragments
show the reaction diagram
amelogenin + H2O
23 kDa amelogenin + 5 kDa tyrosine-rich amelogenin peptide
show the reaction diagram
-
cleaves amelogenin between Trp45 and Leu46
-
-
?
amelogenin + H2O
?
show the reaction diagram
amelogenin + H2O
amelogenin fragments
show the reaction diagram
amelogenin + H2O
amelogenin fragments rH163 + rH146
show the reaction diagram
-
-
in high phosphates conditions (20.9 mM KH2PO4) no cleavage site is observed in the central region of residues Q54–P146, which also shows the slowest cleavage rate with the maximum accumulation of fragment rH163 at 4 h time-point. In the no calcium and phosphates conditions, the accumulation of rH163 reaches the maximum amount at 1 h and the cleavage in the central region Q54-P146 appears only after 5 h. Under high calcium conditions (33.4 mM CaCl2), the fastest cleavage rate is observed and also few exclusive and additional cleavage sites at T61, H67. Other conditions also show some exclusive cleavage sites such as P2 for no calcium and phosphates, P50 for low calcium and phosphates and G10 for high calcium and phosphates. The N-terminal positions Y11, N13, F14, S15, E17, K23, W24, P33, G42, and S53 and the C-terminal positions P155 and T158 are cleaved in all conditions used
-
?
amelogenin + H2O
fragments of amelogenin
show the reaction diagram
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-
-
-
?
amylogenin + H2O
4 major peptide fragments of MWs 24 kDa, 23 kDa, 22 kDa, and 20 kDa
show the reaction diagram
-
-
?
amylogenin + H2O
?
show the reaction diagram
cartilage oligomeric matrix protein + H2O
60 kDa protein
show the reaction diagram
100 kDa protein substrate
-
?
casein + H2O
?
show the reaction diagram
dentin sialophosphoprotein + H2O
dentin sialoprotein-glycoprotein + dentin phosphoprotein
show the reaction diagram
-
-
-
-
?
dentin sialoprotein-glycoprotein + H2O
dentin sialoprotein + dentin glycoprotein
show the reaction diagram
-
-
-
-
?
E-cadherin + H2O
?
show the reaction diagram
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MMP20 cleaves the extracellular domain of E-cadherin
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-
?
enamel protein + H2O
?
show the reaction diagram
-
MMP-20 is secreted along with enamel proteins by secretory stage ameloblasts into the enamel matrix of developing teeth. Enamel protein cleavage products accumulate in the space between the crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated enamel proteins, so their concentration decreases with depth. The principle functions of MMP-20 in dental enamel formation is to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins
-
-
?
enamelin + H2O
enamelin fragments
show the reaction diagram
-
-
-
-
?
endostatin + H2O
peptides
show the reaction diagram
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comparison of efficiency to several other proteinases
-
?
leucine-rich amylogenin peptide + H2O
leucine-rich amylogenin residues 181-186 + leucine-rich amylogenin residues 187-188
show the reaction diagram
corresponds to residues 181-188 of amylogenin, recombinant enzyme, cleavage site is P186-A187
-
?
Mca-KPLGL-Dpa-AR-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Mca-PLA-norvaline-Dpa-AR-NH2 + H2O
?
show the reaction diagram
synthetic fluorogenic substrate
-
?
Mca-PLGL-Dpa-AR + H2O
?
show the reaction diagram
Mca-PLGL-Dpa-AR-NH2 + H2O
?
show the reaction diagram
Mca-PLGL-[3-DNP-2,3-DAP]-AR-NH2 + H2O
?
show the reaction diagram
Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
proteins + H2O
peptides
show the reaction diagram
type V collagen + H2O
?
show the reaction diagram
-
-
-
-
?
tyrosine-rich amylogenin peptide + H2O
tyrosine-rich amylogenin residues 36-45 + tyrosine-rich amylogenin residues 46-49
show the reaction diagram
corresponds to residues 36-49 of amylogenin, recombinant enzyme, cleavage site is W45-L46
-
?
dentin sialoprotein + H2O
additional information
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
aggrecan + H2O
?
show the reaction diagram
O60882
cleavage site is Asn341-Phe342
-
?
ameloblastin + H2O
?
show the reaction diagram
P79287
MMP-20 processes ameloblastin during the secretory stage of amelogenesis, cleaves glycosylated recombinant porcine ameloblastin after Pro2, Gln130, Gln139, Arg170, and Ala222. MMP-20 generates the 23-kDa ameloblastin starting at Tyr223, as well as the 17-kDa (Val1-Arg170) and 15-kDa (Val1-Gln130) ameloblastin cleavage products that concentrate in the sheath space during the secretory stage
-
-
?
ameloblastin + H2O
ameloblastin fragments
show the reaction diagram
-
N-terminal ameloblastin cleavage products of 13, 15, and 17 kDa accumulate in the sheath space throughout the enamel layer
-
-
?
amelogenin + H2O
?
show the reaction diagram
amelogenin + H2O
amelogenin fragments
show the reaction diagram
-
-
-
-
?
amelogenin + H2O
fragments of amelogenin
show the reaction diagram
-
-
-
-
?
amylogenin + H2O
?
show the reaction diagram
cartilage oligomeric matrix protein + H2O
60 kDa protein
show the reaction diagram
O60882
100 kDa protein substrate
-
?
E-cadherin + H2O
?
show the reaction diagram
-
MMP20 cleaves the extracellular domain of E-cadherin
-
-
?
enamel protein + H2O
?
show the reaction diagram
-
MMP-20 is secreted along with enamel proteins by secretory stage ameloblasts into the enamel matrix of developing teeth. Enamel protein cleavage products accumulate in the space between the crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated enamel proteins, so their concentration decreases with depth. The principle functions of MMP-20 in dental enamel formation is to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins
-
-
?
enamelin + H2O
enamelin fragments
show the reaction diagram
-
-
-
-
?
proteins + H2O
peptides
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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neither calcium nor magnesium alone can effectively activate the proenzyme
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
hydroxyapatite
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marimastat
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alters morphogenesis and mineralization of the tooth germs associated with inhibition of activation of MMP-20
N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid
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NaF
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0.01 mM NaF downregulates the synthesis of MMP-20 by 21%
NNGH
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SYGYEPMGGWLHHQ
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competive against Mca-KPLGL-Dpa-AR-NH2
SYGYETMGGWLHHQ
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competive against Mca-KPLGL-Dpa-AR-NH2
tissue matrix metalloprotease inhibitor TIMP-2
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additional information
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inhibitor design, determination of the features of the individual binding pockets of the enzyme
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0195 - 0.585
amelogenin
-
0.0143 - 0.0164
Mca-PLGL-Dpa-AR
0.0143 - 0.0164
Mca-PLGL-[3-DNP-2,3-DAP]-AR-NH2
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.031 - 0.77
amelogenin
-
8.1 - 9
Mca-PLGL-Dpa-AR
8.1 - 9
Mca-PLGL-[3-DNP-2,3-DAP]-AR-NH2
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.8 - 1.9
amelogenin
22282
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
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assay at
7.5
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assay at
7.6
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
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assay at room temperature
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
minute quantities, 5000fold lower than in 4-day-old first molar tooth buds
Manually annotated by BRENDA team
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from mouse embryos at E18.5 and postnatal day 3 mice
Manually annotated by BRENDA team
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presence of MMP20 at mRNA and protein level. MMP20 is coexpressed with dentin sialophosphoprotein DSPP. The MMP20-DSPP interaction is very intense and specific, and precludes MMP20 from interacting with the other members of the small integrin-binding ligand N-linked glycoproteins
Manually annotated by BRENDA team
only in jaw containing the developing tooth buds appreciable levels of the enzyme
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
mainly cytosolic in the presecretory and late stage ameloblasts and odontoblasts
Manually annotated by BRENDA team
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mainly nuclear in the presecretory ameloblasts and odontoblasts
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
21000
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Western blot analysis, active form of MMP-20
41000
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zymography, active form
46000
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zymography or Western blot analysis, active form
57000
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recombinant enzyme, gel filtration
78000
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zymography or Western blot analysis, MMP-20/TIMP-2 complex
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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structure analysis and modeling
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
solution structure of the catalytic domain of MMP-20 complexed with N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the addition of 1 mM EDTA into activation buffer can protect the 55 kDa proenzyme from autolysis and degradation
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; nickel resin chromatography
; recombinant wild-type and inactive mutant E227A
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anion exchange chromatography and gel filtration
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His-TRAP chelating nickel affinity column chromatography
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native enzyme from soft enamel-alkaline extract by anion exchange chromatography, ultrafiltration, and heparin affinity chromatography
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Ni-NTA column chromatography
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purified on Ni column
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Q-Sepharose column chromatography and heparin Sepharose 6 column chromatography
recombinant from Escherichia coli
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recombinant His-tagged MMP-20 by metal affinity chromatography
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recombinant His-tagged pro-enzyme from Escherichia coli
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, chromosome mapping to 11q22, expression in Escherichia coli BL21(DE3)
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expressed in Escherichia coli
expressed in Escherichia coli BL21(DE3) cells; expression in Escherichia coli
expressed in Escherichia coli BL21(DE3) pLysS cells
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expressed in Escherichia coli XL1-Blue cells
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expressed in Escherichia coli XL1-Blue cells; expression in human kidney 293F cells
expression in Escherichia coli
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expression in Escherichia coli as an N-terminal His6 fusion
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expression in Escherichia coli XL-1 Blue as a His-tagged protein
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expression of His-tagged MMP-20
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isolation, characterization, and chromosomal location mapping of the mouse enamelysin gene locus
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MMP20 DNA and amino acid sequenced determination and analysis, genotyping
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MMP20 gene, DNA and amino acid sequence determination and analysis, allele-specific expression method, genotyping
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overexpression of His-atgged pro-enzyme in Escherichia coli BL21(DE3)
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real-time PCR MMP-20 expression analysis, overview
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
increased expression of ODAM and Runx2 augments MMP-20 expression, and both TGF-beta1 and BMP-2 up-regulate Runx2 expression. TGF-beta1 promotes MMP-20 expression in ameloblasts
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loss and siRNA-mediated silencing of Runx2 in ameloblast-lineage cells decreases ODAM expression, resulting in downregulation of MMP-20 expression
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Mmp20 expression levels must be within a specific range for normal enamel development to occur. Creation of a normally thick enamel layer may occur over a wider range of Mmp20 expression levels, but acquisition of normal enamel hardness has a narrower range
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transforming growth factor-beta1, TGF-beta1, prominently induces MMP20 expression in ameloblast-lineage cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E227A
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inactive; inactive mutant enzyme
E235A
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enzymatically inactive MMP-20
H226Q
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the missense mutation does not interfere with MMP20 expression, but completely abolish MMP-20 proteolytic activity. The enamel phenotype is an autosomal-recessive hypomaturation type of amelogenesis imperfecta
W34X
-
the nonsense mutation results in no functional MMP20 during tooth formation
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from inclusion bodies expressed in Escherichia coli
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renaturation from inclusion bodies after overexpression in Escherichia coli
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
degradation
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MMP-20 processes dentin sialophosphoprotein into smaller subunits in the dentin matrix during odontogenesis
medicine
pharmacology
-
enzyme is a potential target for selective inhibition and inhibitor design
additional information