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Literature summary for 3.4.24.80 extracted from

  • Pahwa, S.; Bhowmick, M.; Amar, S.; Cao, J.; Strongin, A.Y.; Fridman, R.; Weiss, S.J.; Fields, G.B.
    Characterization and regulation of MT1-MMP cell surface-associated activity (2019), Chem. Biol. Drug Des., 93, 1251-1264 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene MMP14, recombinant expression of wild-type enzyme, a soluble enzyme form, and different enzyme MT1-MMP domain constructs in MCF-7 cells, overview Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information deletion of the MT1-MMP cytoplasmic tail or deletion of the hemopexin-like domain Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
THP-1
-
Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0151
-
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 pH not specified in the publication, 37°C, recombinant wild-type membrane-bound enzyme Homo sapiens
0.0186
-
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 pH not specified in the publication, 37°C, recombinant soluble enzyme Homo sapiens
0.0234
-
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 pH not specified in the publication, 37°C, recombinant enzyme mutant lacking the C-terminal domain Homo sapiens
0.0368
-
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 pH not specified in the publication, 37°C, recombinant enzyme mutant lacking the HPX domain Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cell surface
-
Homo sapiens 9986
-
membrane
-
Homo sapiens 16020
-
additional information quantitative assessment of MT1-MMP cell surface-associated proteolytic activity compared to soluble activity. MT1-MMP activity (kcat/KM) on the cell surface is 4.8fold lower compared with soluble MT1-MMP, with the effect largely manifested in kcat. Deletion of the MT1-MMP cytoplasmic tail enhances cell surface activity, with both kcat and KM values affected, while deletion of the hemopexin-like domain negatively impacts KM and increases kcat. Cell surface localization of MT1-MMP restricts substrate binding and protein-coupled motions (based on changes in both kcat and KM) for catalysis Homo sapiens
-
-

Metals/Ions

Metals/Ions Comment Organism Structure
Zn2+ a zinc-dependent endopeptidase Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
Collagen + H2O Homo sapiens
-
?
-
?
proMMP-2 + H2O Homo sapiens
-
MMP-2 + pro-peptide
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P50281
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
proteolytic modification MT1-MMP is activated by incubation of the proMT-MMP with rhTrypsin-3 for 1 hr at 37°C Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
mesenchymal stem cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 + H2O triple-helical substrate fTHP-9 Homo sapiens (Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly + Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2
-
?
Collagen + H2O
-
Homo sapiens ?
-
?
dabcyl-Gly-Gly-Pro-Gln-Gly-Ile-Trp-Gly-Gln-Lys(fluorescein)-Ahx-Cys + H2O
-
Homo sapiens ?
-
?
proMMP-2 + H2O
-
Homo sapiens MMP-2 + pro-peptide
-
?

Subunits

Subunits Comment Organism
? x * 65000, pro-MT1-MMP, SDS-PAGE, x * 57000, mature sMT1-MMP, SDS-PAGE Homo sapiens
More MT1-MMP domain structure, overview Homo sapiens

Synonyms

Synonyms Comment Organism
MT1-MMP
-
Homo sapiens
sMT1-MMP
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.14
-
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 pH not specified in the publication, 37°C, recombinant wild-type membrane-bound enzyme Homo sapiens
0.2
-
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 pH not specified in the publication, 37°C, recombinant enzyme mutant lacking the HPX domain Homo sapiens
0.21
-
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 pH not specified in the publication, 37°C, recombinant enzyme mutant lacking the C-terminal domain Homo sapiens
0.84
-
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 pH not specified in the publication, 37°C, recombinant soluble enzyme Homo sapiens

General Information

General Information Comment Organism
malfunction deletion of the MT1-MMP cytoplasmic tail enhances cell surface activity, with both kcat and KM values affected, while deletion of the hemopexin-like domain negatively impacts KM and increases kcat Homo sapiens
additional information visualization of membrane-bound, active MT1-MMP is achieved by fluorescence resonance energy transfer (FRET) imaging of surface-anchored sensors. An initial MT1-MMP sensor was created using the Cys-Pro-Lys-Glu-Ser-Cys-Asn-Leu-Phe-Val-Leu-Lys-Asp sequence, derived from the MT1-MMP cleavage site in proMMP-2. The C-terminus plays a required role in regulating proteolytic activity at the cell surface Homo sapiens
physiological function cell surface localization of MT1-MMP restricts substrate binding and protein-coupled motions (based on changes in both kcat and KM) for catalysis Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
5.44
-
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 pH not specified in the publication, 37°C, recombinant enzyme mutant lacking the HPX domain Homo sapiens
8.97
-
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 pH not specified in the publication, 37°C, recombinant enzyme mutant lacking the C-terminal domain Homo sapiens
9.27
-
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 pH not specified in the publication, 37°C, recombinant wild-type membrane-bound enzyme Homo sapiens
45.2
-
(Gly-Pro-Hyp)5-Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly-Cys(Mob)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp)5-NH2 pH not specified in the publication, 37°C, recombinant soluble enzyme Homo sapiens