Structural Analysis of HIV-1 CRF01_AE Protease in Complex with the Substrate p1-p6

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA; Laboratory of Therapeutic Research and Clinical Science, AIDS Research Center, National Institute of Infectious Diseases, 4-7-1 Gakuenn Musashimurayama, Tokyo 208-0011, Japan

^* To whom correspondence should be addressed. Email: Celia.Schiffer{at}umassmed.edu.

	Abstract

The effect of amino acid variability between human immunodeficiency virus type-1 (HIV-1) clades on structure and the emergence of resistance mutations in HIV-1 protease has become an area of significant interest in recent years. We determined the first crystal structure of HIV-1 CRF01_AE protease in complex with the p1-p6 substrate determined to a resolution of 2.8 Å. Hydrogen bonding between the flap hinge and protease core regions show significant structural rearrangements in CRF01_AE protease when compared to the clade B protease structure.