Title
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
2007-06-29
Document Type
Article
Subjects
Binding Sites; Crystallography, X-Ray; HIV Protease; HIV Protease Inhibitors; Models, Molecular; Protein Structure, Tertiary; Sulfonamides
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
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
10.1128/JVI.00799-07
Source
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
PubMed ID
17596316
Repository Citation
Nalam MN, Peeters A, Jonckers TH, Dierynck I, Schiffer CA. (2007). Crystal structure of lysine sulfonamide inhibitor reveals the displacement of the conserved flap water molecule in human immunodeficiency virus type 1 protease. Open Access Publications by UMass Chan Authors. https://doi.org/10.1128/JVI.00799-07. Retrieved from https://escholarship.umassmed.edu/oapubs/1314