HIV-1 Protease Mutations and Inhibitor Modifications Monitored on a Series of Complexes. Structural Basis for the Effect of the A71V Mutation on the Active Site

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• 作者：Tereza Ská ; lová ; Jan Dohná ; lek ; Jarmila Du//pubs.acs.org/images/entities/scaron.gif" border="0">ková ; Hana Petroková ; Martin Hrad&iacute ; lek ; Milan Sou<
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：September 21, 2006
• 年：2006
• 卷：49
• 期：19
• 页码：5777 - 5784
• 全文大小：463K
• 年卷期：v.49,no.19(September 21, 2006)
• ISSN：1520-4804

文摘

Two new X-ray structures of an HIV-1 protease mutant (A71V, V82T, I84V) in complex with inhibitorsSE and SQ, pseudotetrapeptide inhibitors with an acyclic S-hydroxyethylamine isostere, were determined.Comparison of eight structures exploring the binding of four similar inhibitors-SE, SQ (S-hydroxyethylamineisostere), OE (ethyleneamine), and QF34 (hydroxyethylene)-to wild-type and A71V/V82T/I84V HIV-1protease elucidates the principles of altered interaction with changing conditions. The A71V mutation, whichis distant from the active site, causes changes in the structure of the enzyme detectable by the means ofX-ray structure analysis, and a route of propagation of the effect toward the active site is proposed.