title: Joint X-ray/neutron crystallographic study of HIV-1 protease with clinical inhibitor amprenavir: insights for drug design.
abstract: HIV-1 protease is an important target for the development of antiviral inhibitors to treat AIDS. A room-temperature joint X-ray/neutron structure of the protease in complex with clinical drug amprenavir has been determined at 2.0 Å resolution. The structure provides direct determination of hydrogen atom positions in the enzyme active site. Analysis of the enzyme-drug interactions suggests that some hydrogen bonds may be weaker than deduced from the non-hydrogen interatomic distances. This information may be valuable for the design of improved protease inhibitors.
authors.affiliation: Departments of Chemistry and Biology, Georgia State University , Atlanta, Georgia, United States.
authors.forename: Irene T
authors.initials: IT
authors.lastname: Weber
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Waltman
authors.forename: Marat
authors.initials: M
authors.lastname: Mustyakimov
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Blakeley
authors.forename: David A
authors.initials: DA
authors.lastname: Keen
authors.forename: Arun K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Paul
authors.initials: P
authors.lastname: Langan
authors.forename: Andrey Y
authors.initials: AY
authors.lastname: Kovalevsky
mesh_terms: D002219:Carbamates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015195:Drug Design; D005663:Furans; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D033363:Neutron Diffraction; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1