Crystallization of a non-B and a B mutant HIV protease

Autor(es)

Martins, Nádia Helena ; Calazans, Alexandre ; Brindeiro, Rodrigo de Moraes ; Tanuri, Amilcar ; Antunes, Octavio Augusto Ceva ; Polikarpov, Igor ; Sanches, Mario ^[7]

• Tipo de documento: Artigo Científico
• Fonte: ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY; v. 60, n. 9, p. 1625-1627, Sept. 2004.
• Área do conhecimento: Ciências Biológicas - Bioquímica
• Assunto(s): Cristalografia HIV

Resumo

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 22. X-ray diffraction data were collected from these crystals to resolutions of 2.1 and 2.6 Å 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. (AU)

• Processo FAPESP: 00/03674-2 - Cristalografia de raios-X de proteases de HIVs e seus complexos com inibidores
• Beneficiário: Mario Sanches Matilde Junior
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 03/09461-9 - Producao heterologa de proteases de hiv de subtipos brasileiros para estudos cristalograficos e enzimaticos.
• Beneficiário: Nádia Helena Martins
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 99/03387-4 - Estudos estruturais de proteínas usando luz síncrotron
• Beneficiário: Igor Polikarpov
• Modalidade de apoio: Auxílio à Pesquisa - Temático