Structural Analysis of the Native and Drug­ Resistant HIV-1 Proteinases Complexed With an Aminodiol Inhibitor

Title:Structural Analysis of the Native and Drug­ Resistant HIV-1 Proteinases Complexed With an Aminodiol Inhibitor

Volume: 3 Issue: 6

Author(s): Jukka Kervinen, Narmada Thanki, Alexander Zdanov, Joseph Tino, Joel Barrish, Pin Fang Lin, Richard Colonno, Keith Riccardi, Himadri Samanta and Alexander Wlodawer*

Affiliation:

• Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Frederick, MD 21702, USA

Abstract: Crystal structures of the native HIV-1 proteinase and an A71TN82A mutant have been solved in complexes with a symmetric aminodiol inhibitor, BMS-182193. Some of the conformational differences between these two complexes can be traced to their non-isomorphous crystal forms, but numerous rearrangements due to mutations are clearly visible.The V82A mutation creates more space at the periphery of the active site cleft, allowing distal parts of the inhibitor to move more freely, whereas the non-active-site mutation A71T stabilizes the enzyme backbone. The role of mutations in eliciting drug resistance is discussed.

Cite this article as:

Kervinen Jukka, Thanki Narmada, Zdanov Alexander, Tino Joseph, Barrish Joel, Lin Fang Pin, Colonno Richard, Riccardi Keith, Samanta Himadri and Wlodawer Alexander*, Structural Analysis of the Native and Drug­ Resistant HIV-1 Proteinases Complexed With an Aminodiol Inhibitor, Protein & Peptide Letters 1996; 3 (6) . https://dx.doi.org/10.2174/092986650306221101122158