A clogged gutter mechanism for protease inhibitors

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A clogged gutter mechanism for protease inhibitors.

A classical peptide inhibitor of serine proteases that is hydrolyzed approximately 10(7) times more slowly than a good substrate is shown to form an acyl-enzyme intermediate rapidly. Despite this quick first step, further reaction is slowed dramatically because of tight and oriented binding of the cleaved peptide, preventing acyl-enzyme hydrolysis and favoring the reverse reaction. Moreover, th...

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Human immunodeficiency virus type 1 (HIV-1) protease inhibitors comprise an important class of drugs used in HIV treatments. However, mutations of protease genes accelerated by low fidelity of reverse transcriptase yield drug resistant mutants of reduced affinities for the inhibitors. This problem is considered to be a serious barrier against HIV treatment for the foreseeable future. In this st...

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Translocation into the endoplasmic reticulum (ER) is the first step in the biogenesis of thousands of eukaryotic endomembrane proteins. Although functional ER translocation has been avidly studied, little is known about the quality control mechanisms that resolve faulty translocational states. One such faulty state is translocon clogging, in which the substrate fails to properly translocate and...

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resistance mechanism of human immunodeficiency virus type-1 protease to inhibitors: a molecular dynamic approach

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ژورنال

عنوان ژورنال: Proceedings of the National Academy of Sciences

سال: 2002

ISSN: 0027-8424,1091-6490

DOI: 10.1073/pnas.112332899