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Literature summary for 3.4.21.109 extracted from

  • Maurer, E.; Sisay, M.; Stirnberg, M.; Steinmetzer, T.; Bajorath, J.; Guetschow, M.
    Insights into matriptase-2 substrate binding and inhibition mechanisms by analyzing active-site-mutated variants (2012), ChemMedChem, 7, 68-72.
    View publication on PubMed
Search for more literature for 3.4.21.109

Application

Application Comment Organism
drug development matriptase-2 represents a target for the development of inhibitors, potentially useful in the treatment of hemochromatosis or beneficial as pharmacological tools Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene TMPRSS6, expression of C-terminally c-Myc-tagged wild-type and mutant enzymes in HEK-293 cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
A757S site-directed mutagenesis, the mutant shows altered sensitivity to inhibition by prototype low-molecular weight ligands compared to the wild-type enzyme Homo sapiens
A757S/L785S site-directed mutagenesis, the mutant shows altered sensitivity to inhibition by prototype low-molecular weight ligands compared to the wild-type enzyme Homo sapiens
E712Y site-directed mutagenesis, the mutant shows altered sensitivity to inhibition by prototype low-molecular weight ligands compared to the wild-type enzyme Homo sapiens
E712Y/A757S/L785S site-directed mutagenesis, the mutant shows altered sensitivity to inhibition by prototype low-molecular weight ligands compared to the wild-type enzyme Homo sapiens
H665F site-directed mutagenesis, the mutant shows altered sensitivity to inhibition by prototype low-molecular weight ligands compared to the wild-type enzyme Homo sapiens
L785S site-directed mutagenesis, the mutant shows altered sensitivity to inhibition by prototype low-molecular weight ligands compared to the wild-type enzyme Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information analysis of interaction of matriptase-2 with prototype low-molecular weight ligands using site-directed mutagenesis, kinetic analysis and molecular modeling, substrate/inhibitor-enzyme interactions, overview Homo sapiens
N-(benzylsulfonyl)-3-cyclohexylalanyl-N-(4-carbamimidoylbenzyl)-L-prolinamide inhibitor modeling in the wild-type enzyme active site, overview Homo sapiens
N-(benzylsulfonyl)-3-cyclohexylalanyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide
-
 Homo sapiens
N2-(benzylsulfonyl)arginyl-N-(4-carbamimidoylbenzyl)-L-prolinamide
-
 Homo sapiens
N2-(benzylsulfonyl)arginyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide
-
 Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.024
-
 Boc-Gln-Ala-Arg-4-nitroanilide pH and temperature not specified in the publication, recombinant c-Myc-tagged mutant H665F Homo sapiens
0.19
-
 Boc-Gln-Ala-Arg-4-nitroanilide pH and temperature not specified in the publication, recombinant c-Myc-tagged mutant A757S Homo sapiens
0.21
-
 Boc-Gln-Ala-Arg-4-nitroanilide pH and temperature not specified in the publication, recombinant c-Myc-tagged wild-type enzyme Homo sapiens
0.38
-
 Boc-Gln-Ala-Arg-4-nitroanilide pH and temperature not specified in the publication, recombinant c-Myc-tagged mutant Homo sapiens
0.62
-
 Boc-Gln-Ala-Arg-4-nitroanilide pH and temperature not specified in the publication, recombinant c-Myc-tagged mutant L785S Homo sapiens
0.83
-
 Boc-Gln-Ala-Arg-4-nitroanilide pH and temperature not specified in the publication, recombinant c-Myc-tagged mutant A757S/L785S Homo sapiens
1
-
 Boc-Gln-Ala-Arg-4-nitroanilide above, pH and temperature not specified in the publication, recombinant c-Myc-tagged mutant E712Y Homo sapiens
1
-
 Boc-Gln-Ala-Arg-4-nitroanilide above, pH and temperature not specified in the publication, recombinant c-Myc-tagged mutant E712Y/A757S/L785S Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cell surface
-
 Homo sapiens 9986
-

Organism

Organism UniProt Comment Textmining
Homo sapiens Q8IU80 gene TMPRSS6
-
Homo sapiens Q9Y5Y6
-
-

Reaction

Reaction Comment Organism Reaction ID
cleaves various synthetic substrates with Arg or Lys at the P1 position and prefers small side-chain amino acids, such as Ala and Gly, at the P2 position the basic group of the P1 arginine side chain makes a salt bridge with Asp 756 at the bottom of the S1 pocket, substrate docking study,overview Homo sapiens
a

Source Tissue

Source Tissue Comment Organism Textmining
epithelial cell
-
 Homo sapiens
-
liver matriptase-2 is predominantly expressed in the liver Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
Boc-Gln-Ala-Arg-4-nitroanilide + H2O
-
 Homo sapiens Boc-Gln-Ala-Arg + 4-nitroaniline
-
 ?

Synonyms

Synonyms Comment Organism
matriptase-2
-
 Homo sapiens
membrane-type serine protease 1
-
 Homo sapiens
MT-SP1
-
 Homo sapiens
MT2
-
 Homo sapiens
suppressor of tumorigenicity 14 protein
-
 Homo sapiens
TMPRSS6
-
 Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000046
-
 N2-(benzylsulfonyl)arginyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant H665F Homo sapiens
0.000052
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant H665F Homo sapiens
0.000055
-
 N2-(benzylsulfonyl)arginyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C Homo sapiens
0.00016
-
 N2-(benzylsulfonyl)arginyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant A757S Homo sapiens
0.00019
-
 N2-(benzylsulfonyl)arginyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged wild-type enzyme Homo sapiens
0.00021
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant A757S Homo sapiens
0.00022
-
 N2-(benzylsulfonyl)arginyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C Homo sapiens
0.00029
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged wild-type enzyme Homo sapiens
0.00077
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C Homo sapiens
0.0012
-
 N2-(benzylsulfonyl)arginyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant L785S Homo sapiens
0.0016
-
 N2-(benzylsulfonyl)arginyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant A757S/L785S Homo sapiens
0.0021
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C Homo sapiens
0.0026
-
 N2-(benzylsulfonyl)arginyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant H665F Homo sapiens
0.003
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant H665F Homo sapiens
0.015
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant L785S Homo sapiens
0.02
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant A757S/L785S Homo sapiens
0.02
-
 N2-(benzylsulfonyl)arginyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant E712Y Homo sapiens
0.02
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant E712Y Homo sapiens
0.03
-
 N2-(benzylsulfonyl)arginyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant E712Y/A757S/L785S Homo sapiens
0.03
-
 N2-(benzylsulfonyl)arginyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged wild-type enzyme Homo sapiens
0.037
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged wild-type enzyme Homo sapiens
0.054
-
 N2-(benzylsulfonyl)arginyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant L785S Homo sapiens
0.069
-
 N2-(benzylsulfonyl)arginyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant A757S Homo sapiens
0.075
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant A757S Homo sapiens
0.1
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-(4-carbamimidoylbenzyl)-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant E712Y/A757S/L785S Homo sapiens
0.2
-
 N2-(benzylsulfonyl)arginyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant E712Y Homo sapiens
0.2
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant E712Y Homo sapiens
0.2
-
 N2-(benzylsulfonyl)arginyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant E712Y/A757S/L785S Homo sapiens
0.2
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant E712Y/A757S/L785S Homo sapiens
0.22
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant L785S Homo sapiens
0.28
-
 N-(benzylsulfonyl)-3-cyclohexylalanyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant A757S/L785S Homo sapiens
0.62
-
 N2-(benzylsulfonyl)arginyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide pH 8.0, 37°C, recombinant c-Myc-tagged mutant A757S/L785S Homo sapiens

General Information

General Information Comment Organism
evolution matriptase shares high sequence similarity with matriptase-2, particularly in the catalytic domain which is about 45% identical Homo sapiens
evolution matriptase-2 belongs to the family of type II transmembrane serine proteases, representing an emerging class of cell surface proteolytic enzymes. Matriptase-2 shares high sequence similarity with matriptase, particularly in the catalytic domain which is about 45% identical Homo sapiens
additional information structural differences between matriptase-2 and matriptase, the enzyme-ligand interactions of matriptase-2 involve four important amino acids, His 665, Glu 712, Ala 757, Leu785. In the active site, matriptase-2 and matriptase vary in relevant amino acids participating in the formation of the S1 and S2 pockets and the S3/S4 binding region. Location of His665, Glu712, Ala757 and Leu785 in the active site of matriptase-2, overview Homo sapiens
additional information structural differences between matriptase-2 and matriptase. In the active site, matriptase-2 and matriptase vary in relevant amino acids participating in the formation of the S1 and S2 pockets and the S3/S4 binding region Homo sapiens
physiological function matriptase is involved in tumor pathogenesis Homo sapiens
physiological function the enzyme suppresses the expression of hepcidin, the main regulator of systemic iron homeostasis, through cleavage of the bone morphogenetic protein co-receptor hemojuvelin, matriptase-2 plays an important role in iron homeostasis Homo sapiens