Crystal structure of lysine sulfonamide inhibitor reveals the displacement of the conserved flap water molecule in human immunodeficiency virus type 1 protease

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



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.

DOI of Published Version



J Virol. 2007 Sep;81(17):9512-8. Epub 2007 Jun 27. Link to article on publisher's site

Journal/Book/Conference Title

Journal of virology

Related Resources

Link to Article in PubMed

PubMed ID