
<ArticleTitle>Discovery of a new inhibitor lead of adenovirus proteinase: steps toward selective, irreversible inhibitors of cysteine proteinases.</ArticleTitle>
<AbstractText>Using the computer docking program EUDOC, in silico screening of a chemical database for inhibitors of <prot>human adenovirus cysteine proteinase</prot> (<prot>hAVCP</prot>) identified 2,4,5,7-tetranitro-9-fluorenone that selectively and irreversibly inhibits <prot>hAVCP</prot> in a two-step reaction: reversible binding (Ki = 3.09 microM) followed by irreversible inhibition (ki = 0.006 s(-1)). The reversible binding is due to molecular complementarity between the inhibitor and the active site of <prot>hAVCP</prot>, which confers the selectivity of the inhibitor. The irreversible inhibition is due to substitution of a nitro group of the inhibitor by the nearby Cys122 in the active site of <prot>hAVCP</prot>. These findings suggest a new approach to selective, irreversible inhibitors of cysteine proteinases involved in normal and abnormal physiological processes ranging from embryogenesis to apoptosis and pathogen invasions.</AbstractText>
