title: Crystallization of a non-B and a B mutant HIV protease.
abstract: HIV polymorphism is responsible for the selection of variant viruses resistant to inhibitors used in AIDS treatment. Knowledge of the mechanism of resistance of those viruses is determinant to the development of new inhibitors able to stop, or at least slow down, the disease's progress caused by new mutations. In this paper, the crystallization and preliminary crystallographic structure solution for two multi-resistant 99 amino acid HIV proteases, both isolated from Brazilian patients failing intensive anti-AIDS therapy are presented, viz. the subtype B mutant, with mutations Q7K, S37N, R41K, K45R, I54V, L63P, A71V, V82A and L90M, and the subtype F (wild type), naturally carrying mutations Q7K, I15V, E35D, M36I, S37N, R41K, R57K, D60E, Q61N, I62V, L63S, I64L and L89M, with respect to the B consensus sequence. Both proteins crystallized as a complex with the inhibitor TL-3 in space group P6(1)22. X-ray diffraction data were collected from these crystals to resolutions of 2.1 and 2.6 A for the subtype B mutant and subtype F wild type, respectively, and the enzyme structures were solved by molecular replacement. The crystals of subtype F HIV protease are, to the best of the authors' knowledge, the first protein crystals obtained for a non-B HIV protease.
authors.affiliation: Crystallography Group, Physics Department, USP, São Carlos, SP, Brazil.
authors.forename: Mario
authors.initials: M
authors.lastname: Sanches
authors.forename: Nádia Helena
authors.initials: NH
authors.lastname: Martins
authors.forename: Alexandre
authors.initials: A
authors.lastname: Calazans
authors.forename: Rodrigo de Moraes
authors.initials: Rde M
authors.lastname: Brindeiro
authors.forename: Amilcar
authors.initials: A
authors.lastname: Tanuri
authors.forename: Octavio Augusto Ceva
authors.initials: OA
authors.lastname: Antunes
authors.forename: Igor
authors.initials: I
authors.lastname: Polikarpov
mesh_terms: D003460:Crystallization; D018360:Crystallography, X-Ray; D003627:Data Interpretation, Statistical; D024882:Drug Resistance, Viral; D016333:HIV Protease / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D008970:Molecular Weight; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D007527:Isoenzymes; D016333:HIV Protease