1Y3G

Crystal Structure of a Silanediol Protease Inhibitor Bound to Thermolysin

1Y3G の概要

• エントリーDOI: 10.2210/pdb1y3g/pdb
• 分子名称: Thermolysin, CALCIUM ION, ZINC ION, ... (8 entities in total)
• 機能のキーワード: silanediol protease inhibitor, thermolysin, hydrolase
• 由来する生物種: Bacillus thermoproteolyticus
• 細胞内の位置: Secreted: P00800
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35213.00

構造登録者

Juers, D.H.,Kim, J.,Matthews, B.W.,Sieburth, S.M. (登録日: 2004-11-24, 公開日: 2006-01-17, 最終更新日: 2024-02-14)

主引用文献

Juers, D.H.,Kim, J.,Matthews, B.W.,Sieburth, S.M.
Structural Analysis of Silanediols as Transition-State-Analogue Inhibitors of the Benchmark Metalloprotease Thermolysin(,).
Biochemistry, 44:16524-16528, 2005

PubMed Abstract: 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.

PubMed: 16342943
DOI: 10.1021/bi051346v

実験手法

X-RAY DIFFRACTION (2.1 Å)