1y3g
From Proteopedia
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Crystal Structure of a Silanediol Protease Inhibitor Bound to Thermolysin
Overview
Dialkylsilanediols have been found to be an effective functional group for, the design of active-site-directed protease inhibitors, including aspartic, (HIV protease) and metallo (ACE and thermolysin) proteases. The use of, silanediols is predicated on its resemblance to the hydrated carbonyl, transition-state structure of amide hydrolysis. This concept has been, tested by replacing the presumed tetrahedral carbon of a thermolysin, substrate with a silanediol group, resulting in an inhibitor with an, inhibition constant K(i) = 40 nM. The structure of the silanediol bound to, the active site of thermolysin was found to have a conformation very, similar to that of a corresponding phosphonamidate inhibitor (K(i) = 10, nM). In both cases, a single oxygen is within bonding distance to the, active-site zinc ion, mimicking the presumed tetrahedral transition state., There are binding differences that appear to be related to the presence or, absence of protons on the oxygens attached to the silicon or phosphorus., This is the first crystal structure of an organosilane bound to the active, site of a protease.
About this Structure
1Y3G is a Single protein structure of sequence from Bacillus thermoproteolyticus with CA, ZN, DMS and 3PL as ligands. Active as Thermolysin, with EC number 3.4.24.27 Full crystallographic information is available from OCA.
Reference
Structural analysis of silanediols as transition-state-analogue inhibitors of the benchmark metalloprotease thermolysin., Juers DH, Kim J, Matthews BW, Sieburth SM, Biochemistry. 2005 Dec 20;44(50):16524-8. PMID:16342943
Page seeded by OCA on Wed Nov 21 06:32:31 2007
