Expression, purification and preliminary X-ray crystallographic studies of the human immunodeficiency virus 1 subtype C protease
- Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610 (United States)
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610 (United States)
Crystals of the human immunodeficiency virus 1 subtype C protease complexed with indinavir and nelfinavir have been grown in the monoclinic space group P2{sub 1} and shown to diffract X-rays to 2.3 Å resolution. Crystals of the human immunodeficiency virus 1 (HIV-1) subtype C protease (PR) complexed with the clinically used inhibitors indinavir (IDV) and nelfinavir (NFV) have been grown in the monoclinic space group P2{sub 1}, with mean unit-cell parameters a = 46.7 (±0.1), b = 59.8 (±0.3), c = 87.0 (±0.4) Å, β = 95.2 (±0.5)°. The crystals of both complexes have been shown to diffract X-rays to 2.3 Å resolution. The diffraction data for the subtype C PR complexes with IDV and NFV were subsequently processed and reduced, with overall R{sub sym} values of 8.4 and 11.4%, respectively. Based on the unit-cell volumes, molecular-replacement results and packing considerations, there are two protease homodimers per crystallographic asymmetric unit in each of the complexes. The data were initially phased using a model based on the crystal structure of HIV-1 subtype B PR; the structures have been determined and further refinement and analysis are in progress. These structures and subsequent studies with other inhibitors will greatly aid in correlating the amino-acid variation between the different HIV PRs and understanding their differential sensitivity and resistance to current drug therapy.
- OSTI ID:
- 22360313
- Journal Information:
- Acta Crystallographica. Section F, Vol. 63, Issue Pt 4; Other Information: PMCID: PMC2330223; PMID: 17401206; PUBLISHER-ID: pu5176; OAI: oai:pubmedcentral.nih.gov:2330223; Copyright (c) International Union of Crystallography 2007; Country of input: International Atomic Energy Agency (IAEA); ISSN 1744-3091
- Country of Publication:
- United Kingdom
- Language:
- English
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