Evaluation of the substrate envelope hypothesis for inhibitors of HIV-1 protease.

Evaluation of the substrate envelope hypothesis for inhibitors of HIV-1 protease. Research Abstract Details 

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Evaluation of the substrate envelope hypothesis for inhibitors of HIV-1 protease. Abstract Text:

Sripriya Chellappan,Visvaldas Kairys,Miguel X Fernandes,Celia Schiffer,Michael K Gilson,

Crystallographic data show that various substrates of HIV protease occupy a remarkably uniform region within the binding site; this region has been termed the substrate envelope. It has been suggested that an inhibitor that fits within the substrate envelope should tend to evade viral resistance because a protease mutation that reduces the affinity of the inhibitor will also tend to reduce the affinity of substrate, and will hence decrease the activity of the enzyme. Accordingly, inhibitors that fit the substrate envelope better should be less susceptible to clinically observed resistant mutations, since these must also allow substrates to bind. The present study describes a quantitative measure of the volume of a bound inhibitor falling outside the substrate envelope, and observes that this quantity correlates with the inhibitor's losses in affinity to clinically relevant mutants. This measure may thus be useful as a penalty function in the design of robust HIV protease inhibitors.

Evaluation of the substrate envelope hypothesis for inhibitors of HIV-1 protease. Publishing Authors By Initials

S Chellappan,V Kairys,MX Fernandes,C Schiffer,MK Gilson,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research

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Evaluation of the substrate envelope hypothesis for inhibitors of HIV-1 protease. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proteins

VOLUME: 68

Page Numbers: 561-7

Journal Abbreviation: Proteins

ISSN: 1097-0134

DAY: 1

MONTH: Aug

YEAR: 2007

Evaluation of the substrate envelope hypothesis for inhibitors of HIV-1 protease. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8700181

Evaluation of the substrate envelope hypothesis for inhibitors of HIV-1 protease. Keywords Mesh Terms:

KEYWORDS: Substrate Specificity

MESH TERMS: metabolism

Chemical & Substance for Abstract: Evaluation of the substrate envelope hypothesis for inhibitors of HIV-1 protease. Information

Substance Name: HIV Protease

Registry Number: EC 3.4.23.-

Grant and Affiliation Information for Evaluation of the substrate envelope hypothesis for inhibitors of HIV-1 protease.

AFFILIATION: Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM66524

ACRONYM: GM

MEDLINETA: Proteins

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