Crystal structure of lysine sulfonamide inhibitor reveals the displacement of the conserved flap water molecule in human immunodeficiency virus type 1 protease
Department of Biochemistry and Molecular Pharmacology
Binding Sites; Crystallography, X-Ray; HIV Protease; HIV Protease Inhibitors; Models, Molecular; Protein Structure, Tertiary; Sulfonamides
Life Sciences | Medicine and Health Sciences
Human immunodeficiency virus type 1 (HIV-1) protease has been continuously evolving and developing resistance to all of the protease inhibitors. This requires the development of new inhibitors that bind to the protease in a novel fashion. Most of the inhibitors that are on the market are peptidomimetics, where a conserved water molecule mediates hydrogen bonding interactions between the inhibitors and the flaps of the protease. Recently a new class of inhibitors, lysine sulfonamides, was developed to combat the resistant variants of HIV protease. Here we report the crystal structure of a lysine sulfonamide. This inhibitor binds to the active site of HIV-1 protease in a novel manner, displacing the conserved water and making extensive hydrogen bonds with every region of the active site.
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Citation: J Virol. 2007 Sep;81(17):9512-8. Epub 2007 Jun 27. Link to article on publisher's site
DOI of Published Version
Journal of virology
Nalam, Madhavi N. L.; Peeters, Anik; Jonckers, Tim H. M.; Dierynck, Inge; and Schiffer, Celia A., "Crystal structure of lysine sulfonamide inhibitor reveals the displacement of the conserved flap water molecule in human immunodeficiency virus type 1 protease" (2007). Open Access Articles. 1314.