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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Martins, Nádia Helena ; Calazans, Alexandre ; Brindeiro, Rodrigo de Moraes ; Tanuri, Amilcar ; Antunes, Octavio Augusto Ceva ; Polikarpov, Igor ; Sanches, Mario [7]
Total Authors: 7
Document type: Journal article
Source: ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY; v. 60, n. 9, p. 1625-1627, Sept. 2004.
Field of knowledge: Biological Sciences - Biochemistry
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 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)

FAPESP's process: 99/03387-4 - Structural studies of the proteins using synchrotron light
Grantee:Igor Polikarpov
Support type: Research Projects - Thematic Grants