Details

Autor(en) / Beteiligte

• Culberson, J.Chris
• Bush, Bruce L.
• Sardana, Vinod V.

Titel

[21] Qualitative study of drug resistance in retroviral protease using structural modeling and site-directed mutagenesis

Ist Teil von

• Methods in Enzymology, 1994, Vol.241, p.385,IN17,393-392,IN19,394

Ort / Verlag

United States: Elsevier Science & Technology

Erscheinungsjahr

1994

Quelle

MEDLINE

Beschreibungen/Notizen

• This chapter describes the construction of a three-dimensional model of a retroviral protease active site. Once constructed, the model can be used to guide which residues to mutate in site-directed mutagenesis experiments. The goal of the modeling and site-directed mutagenesis is to help guide synthetic efforts toward inhibitors that will be insensitive to the mutations that occur in vivo. The chapter describes a method to identify amino acids involved in key enzyme–inhibitor interactions and to determine mutations that lead to changes in specificity. The method assumes no major changes in the binding pocket of the enzyme. A remaining challenge is to design inhibitors that are less sensitive than those discussed here to the individual active site mutations of HIV-1 protease.