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Literature summary for 3.4.24.26 extracted from

  • Adekoya, O.; Sjoeli, S.; Wuxiuer, Y.; Bilto, I.; Marques, S.; Santos, M.; Nuti, E.; Cercignani, G.; Rossello, A.; Winberg, J.; Sylte, I.
    Inhibition of pseudolysin and thermolysin by hydroxamate-based MMP inhibitors (2014), Eur. J. Med. Chem., 89, 340-348.
    View publication on PubMed
Search for more literature for 3.4.24.26

Inhibitors

Inhibitors Comment Organism Structure
2-[(biphenyl-4-ylsulfonyl)[2-(hydroxyamino)-2-oxoethyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
-
 Bacillus thermoproteolyticus
2-[benzyl[2-(hydroxyamino)-2-oxoethyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name) the phenyl group of the strong binder occupies the S'2-subpocket, while a second ring system occupy the S1-subpocket in both thermolysin, EC 3.4.24.27, and pseudolysin Bacillus thermoproteolyticus
2-[benzyl[2-(hydroxyamino)-2-oxoethyl]amino]-N-[3-(4-phenylpiperazin-1-yl)propyl]acetamide (non-preferred name) the phenyl group of the strong binder occupies the S'2-subpocket, while a second ring system occupy the S1-subpocket in both thermolysin, EC 3.4.24.27, and pseudolysin Bacillus thermoproteolyticus
2-[[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
-
 Bacillus thermoproteolyticus
2-[[2-(hydroxyamino)-2-oxoethyl][(4-phenoxyphenyl)sulfonyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
-
 Bacillus thermoproteolyticus
additional information inhibitor synthesis, docking analysis and binding structure, molecular modeling and Molecular dynamics simulation of pseudolysin-ligand interactions, overview. When the compounds possess two ring systems, the largest and most electron rich ring system seems to occupy the S1-subpocket. The fourth zinc coordinating ligand in the free enzyme is a water molecule. Upon inhibitor binding this water molecule is replaced by a metal binding group of the inhibitor Bacillus thermoproteolyticus
N-[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-N-[(4-phenoxyphenyl)sulfonyl]glycine
-
 Bacillus thermoproteolyticus
[(biphenyl-4-ylmethyl)[2-(hydroxyamino)-2-oxoethyl]amino]acetic acid
-
 Bacillus thermoproteolyticus
[(biphenyl-4-ylsulfonyl)[2-(hydroxyamino)-2-oxoethyl]amino]acetic acid
-
 Bacillus thermoproteolyticus
[1-[2-(hydroxyamino)-2-oxoethyl]-2-[3-(4-phenylpiperazin-1-yl)propyl]hydrazinyl]acetic acid
-
 Bacillus thermoproteolyticus
[[(4-methoxyphenyl)sulfonyl](2-oxo-2-[[2-(4-sulfamoylphenyl)ethyl]amino]ethyl)amino]acetic acid
-
 Bacillus thermoproteolyticus
[[2-(hydroxyamino)-2-oxoethyl](4-nitrobenzyl)amino]acetic acid
-
 Bacillus thermoproteolyticus
[[2-(hydroxyamino)-2-oxoethyl](4-phenoxybenzyl)amino]acetic acid
-
 Bacillus thermoproteolyticus
[[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]acetic acid
-
 Bacillus thermoproteolyticus
[[2-(hydroxyamino)-2-oxoethyl][(4-phenoxyphenyl)sulfonyl]amino]acetic acid
-
 Bacillus thermoproteolyticus

Metals/Ions

Metals/Ions Comment Organism Structure
Zn2+ the enzyme has a catalytic zinc ion at the active site cleft with a tetrahedral coordination formed by the two histidines of a HEXXH motif, and a glutamic acid located 18-72 residues C-terminal of the HEXXH motif. The fourth zinc coordinating ligand in the free enzyme is a water molecule Bacillus thermoproteolyticus

Organism

Organism UniProt Comment Textmining
Bacillus thermoproteolyticus
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
7-methoxycoumarin-4-yl-acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(2,4-dinitrophenyl)-OH
-
 Bacillus thermoproteolyticus ?
-
 ?
Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide + H2O
-
 Bacillus thermoproteolyticus ?
-
 ?

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Bacillus thermoproteolyticus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.8
-
 assay at Bacillus thermoproteolyticus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0004
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus 2-[benzyl[2-(hydroxyamino)-2-oxoethyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
0.0028
-
 pH 7.8, 37°C, versus substrate 7-methoxycoumarin-4-yl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(2,4-dinitrophenyl)-OH Bacillus thermoproteolyticus 2-[benzyl[2-(hydroxyamino)-2-oxoethyl]amino]-N-[3-(4-phenylpiperazin-1-yl)propyl]acetamide (non-preferred name)
0.0067
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus 2-[benzyl[2-(hydroxyamino)-2-oxoethyl]amino]-N-[3-(4-phenylpiperazin-1-yl)propyl]acetamide (non-preferred name)
0.015
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus 2-[[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
0.016
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus 2-[[2-(hydroxyamino)-2-oxoethyl][(4-phenoxyphenyl)sulfonyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
0.02
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus [[2-(hydroxyamino)-2-oxoethyl](4-nitrobenzyl)amino]acetic acid
0.031
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus 2-[(biphenyl-4-ylsulfonyl)[2-(hydroxyamino)-2-oxoethyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
0.033
-
 pH 7.8, 37°C, versus substrate 7-methoxycoumarin-4-yl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(2,4-dinitrophenyl)-OH Bacillus thermoproteolyticus 2-[[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
0.046
-
 pH 7.8, 37°C, versus substrate 7-methoxycoumarin-4-yl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(2,4-dinitrophenyl)-OH Bacillus thermoproteolyticus [[2-(hydroxyamino)-2-oxoethyl][(4-phenoxyphenyl)sulfonyl]amino]acetic acid
0.082
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus N-[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-N-[(4-phenoxyphenyl)sulfonyl]glycine
0.121
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus [(biphenyl-4-ylmethyl)[2-(hydroxyamino)-2-oxoethyl]amino]acetic acid
0.15
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus [(biphenyl-4-ylsulfonyl)[2-(hydroxyamino)-2-oxoethyl]amino]acetic acid
0.153
-
 pH 7.8, 37°C, versus substrate 7-methoxycoumarin-4-yl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(2,4-dinitrophenyl)-OH Bacillus thermoproteolyticus [[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]acetic acid
0.169
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus [[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]acetic acid
0.186
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus [[2-(hydroxyamino)-2-oxoethyl][(4-phenoxyphenyl)sulfonyl]amino]acetic acid
0.2
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus [[2-(hydroxyamino)-2-oxoethyl](4-phenoxybenzyl)amino]acetic acid
0.241
-
 pH 7.8, 37°C, versus substrate 7-methoxycoumarin-4-yl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(2,4-dinitrophenyl)-OH Bacillus thermoproteolyticus [(biphenyl-4-ylsulfonyl)[2-(hydroxyamino)-2-oxoethyl]amino]acetic acid
0.276
-
 pH 7.8, 37°C, versus substrate 7-methoxycoumarin-4-yl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(2,4-dinitrophenyl)-OH Bacillus thermoproteolyticus 2-[[2-(hydroxyamino)-2-oxoethyl][(4-phenoxyphenyl)sulfonyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
0.282
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus [[(4-methoxyphenyl)sulfonyl](2-oxo-2-[[2-(4-sulfamoylphenyl)ethyl]amino]ethyl)amino]acetic acid
0.33
-
 pH 7.8, 37°C, versus substrate Abz-Ala-Gly-Leu-Ala-4-nitrobenzylamide Bacillus thermoproteolyticus [1-[2-(hydroxyamino)-2-oxoethyl]-2-[3-(4-phenylpiperazin-1-yl)propyl]hydrazinyl]acetic acid
0.336
-
 pH 7.8, 37°C, versus substrate 7-methoxycoumarin-4-yl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(2,4-dinitrophenyl)-OH Bacillus thermoproteolyticus N-[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-N-[(4-phenoxyphenyl)sulfonyl]glycine
0.43
-
 pH 7.8, 37°C, versus substrate 7-methoxycoumarin-4-yl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(2,4-dinitrophenyl)-OH Bacillus thermoproteolyticus [[2-(hydroxyamino)-2-oxoethyl](4-phenoxybenzyl)amino]acetic acid

General Information

General Information Comment Organism
evolution thermolysin and pseudolysin belong to subclan MA(E) of peptidases, also known as the Glu-zincins, of the matrix metalloproteinases family of zinc-containing endoproteinases with broad substrate specificity and extracellular matrix components are among the substrates Bacillus thermoproteolyticus
additional information the glutamic acid of the HEXXH motif is catalytically important Bacillus thermoproteolyticus