Thermodynamic and structural analysis of HIV protease resistance to darunavir - analysis of heavily mutated patient- derived HIV-1 proteases

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F14%3A10286809" target="_blank" >RIV/00216208:11310/14:10286809 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/14:00427922 RIV/61388963:_____/14:00427922

Result on the web

<a href="http://dx.doi.org/10.1111/febs.12743" target="_blank" >http://dx.doi.org/10.1111/febs.12743</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/febs.12743" target="_blank" >10.1111/febs.12743</a>

Result language

angličtina

Original language name

Thermodynamic and structural analysis of HIV protease resistance to darunavir - analysis of heavily mutated patient- derived HIV-1 proteases

Original language description

We report enzymologic, thermodynamic and structural analyses of a series of six clinically derived mutant HIV proteases (PR) resistant to darunavir. As many as 20 mutations in the resistant PRs decreased the binding affinity of darunavir by up to 13000-fold, mostly because of a less favorable enthalpy of binding that was only partially compensated by the entropic contribution. X-ray structure analysis suggested that the drop in enthalpy of darunavir binding to resistantPR species was mostly the result of a decrease in the number of hydrogen bonds and a loosening of the fit between the inhibitor and the mutated enzymes. The favorable entropic contribution to darunavir binding to mutated PR variants correlated with a larger burial of the nonpolar solvent-accessible surface area upon inhibitor binding. We show that even very dramatic changes in the PR sequence leading to the loss of hydrogen bonds with the inhibitor could be partially compensated by the entropy contribution as a result of

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

<a href="/en/project/GAP207%2F11%2F1798" target="_blank" >GAP207/11/1798: HIV protease inhibitors: mechanism of action and resistance development</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2014

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

FEBS Journal

ISSN

1742-464X

e-ISSN

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Volume of the periodical

281

Issue of the periodical within the volume

7

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

1834-1847

UT code for WoS article

000333676000010

EID of the result in the Scopus database

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