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Literature summary for 3.4.24.27 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 3.4.24.27

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 and pseudolysin, EC 3.4.24.27 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 and pseudolysin, EC 3.4.24.26 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, 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 + H2O a bradykinin-like substrate 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
7.5
-
 assay at Bacillus thermoproteolyticus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.008
-
 pH 7.5, 37°C Bacillus thermoproteolyticus 2-[benzyl[2-(hydroxyamino)-2-oxoethyl]amino]-N-[3-(4-phenylpiperazin-1-yl)propyl]acetamide (non-preferred name)
0.012
-
 pH 7.5, 37°C Bacillus thermoproteolyticus 2-[benzyl[2-(hydroxyamino)-2-oxoethyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
0.067
-
 pH 7.5, 37°C Bacillus thermoproteolyticus 2-[(biphenyl-4-ylsulfonyl)[2-(hydroxyamino)-2-oxoethyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
0.114
-
 pH 7.5, 37°C Bacillus thermoproteolyticus [[2-(hydroxyamino)-2-oxoethyl][(4-phenoxyphenyl)sulfonyl]amino]acetic acid
0.16
-
 pH 7.5, 37°C Bacillus thermoproteolyticus 2-[[2-(hydroxyamino)-2-oxoethyl][(4-phenoxyphenyl)sulfonyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
0.164
-
 pH 7.5, 37°C Bacillus thermoproteolyticus 2-[[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide (non-preferred name)
0.27
-
 pH 7.5, 37°C Bacillus thermoproteolyticus [[2-(hydroxyamino)-2-oxoethyl][(4-methoxyphenyl)sulfonyl]amino]acetic acid
0.44
-
 pH 7.5, 37°C Bacillus thermoproteolyticus [(biphenyl-4-ylsulfonyl)[2-(hydroxyamino)-2-oxoethyl]amino]acetic acid
0.524
-
 pH 7.5, 37°C Bacillus thermoproteolyticus [[2-(hydroxyamino)-2-oxoethyl](4-phenoxybenzyl)amino]acetic acid
0.637
-
 pH 7.5, 37°C Bacillus thermoproteolyticus [[(4-methoxyphenyl)sulfonyl](2-oxo-2-[[2-(4-sulfamoylphenyl)ethyl]amino]ethyl)amino]acetic acid
0.755
-
 pH 7.5, 37°C Bacillus thermoproteolyticus [[2-(hydroxyamino)-2-oxoethyl](4-nitrobenzyl)amino]acetic acid
1
-
 pH 7.5, 37°C Bacillus thermoproteolyticus N-[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-N-[(4-phenoxyphenyl)sulfonyl]glycine
1
-
 pH 7.5, 37°C Bacillus thermoproteolyticus [(biphenyl-4-ylmethyl)[2-(hydroxyamino)-2-oxoethyl]amino]acetic acid
1
-
 pH 7.5, 37°C Bacillus thermoproteolyticus [1-[2-(hydroxyamino)-2-oxoethyl]-2-[3-(4-phenylpiperazin-1-yl)propyl]hydrazinyl]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