Naslov
Novel Mechanism of Elastase Inhibition by beta-Lactams

Autori
Danilovski, Aleksandar ; Vinković, Mladen

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts / Lah, Nina ; Leban, Ivan - Ljubljana : Univerza v Ljubljani, 2000

Skup
9th Slovenian-Croatian Crystallographic Meeting

Mjesto i datum
Gozd Martuljek, SLOVENIA, 15.06.2000. - 17.06.2000

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
beta-lactam; elastase; macromolecular crystallography

Sažetak
Beta-Lactams and their analogues are well established irreversible suicidal inhibitors of a wide range of serine proteases including elastase, DD-peptidase, beta-lactamase, phospholipase A2 and bacterial signal peptidase. Their efficacy as orally active inhibitors has led to their widespread use in the clinic. In all cases the first step in the inhibition process is acylation of the active serine by the beta-lactam ring to generate a covalently bound acyl-enzyme intermediate complex. Deacylation, i.e. hydrolysis of the acyl-enzyme complex yielding free and regenerated enzyme, is usually a second, time limiting step of inhibition. Here we would like to report the discovery of a novel mechanism of elastase inhibition by beta-lactams, which result in a stable, but non-covalently bound complex. In an initial electron density difference map the conserved and unmodified ligand structure could be clearly observed. The excellent quality of the electron density calculated data to a high resolution of 1.30 A could provide a clear insight into this novel mechanism of the inhibition and serve as a starting point for design of a new class of non-covalently bound elastase inhibitors that might resist enzyme reactivation by hydrolysis.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA