skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Expression, purification and preliminary X-ray crystallographic studies of the human immunodeficiency virus 1 subtype C protease

Abstract

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 themore » amino-acid variation between the different HIV PRs and understanding their differential sensitivity and resistance to current drug therapy.« less

Authors:
;  [1];  [2]; ;  [1]
  1. Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610 (United States)
  2. Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610 (United States)
Publication Date:
OSTI Identifier:
22360313
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section F; Journal Volume: 63; Journal 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)
Country of Publication:
United Kingdom
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; CRYSTAL STRUCTURE; CRYSTALS; CURRENTS; DIFFRACTION; RESOLUTION; SENSITIVITY; SPACE GROUPS; STOWING; VARIATIONS

Citation Formats

Coman, Roxana M., Robbins, Arthur, Goodenow, Maureen M., McKenna, Robert, and Dunn, Ben M., E-mail: bdunn@ufl.edu. Expression, purification and preliminary X-ray crystallographic studies of the human immunodeficiency virus 1 subtype C protease. United Kingdom: N. p., 2007. Web. doi:10.1107/S174430910701161X.
Coman, Roxana M., Robbins, Arthur, Goodenow, Maureen M., McKenna, Robert, & Dunn, Ben M., E-mail: bdunn@ufl.edu. Expression, purification and preliminary X-ray crystallographic studies of the human immunodeficiency virus 1 subtype C protease. United Kingdom. doi:10.1107/S174430910701161X.
Coman, Roxana M., Robbins, Arthur, Goodenow, Maureen M., McKenna, Robert, and Dunn, Ben M., E-mail: bdunn@ufl.edu. Sun . "Expression, purification and preliminary X-ray crystallographic studies of the human immunodeficiency virus 1 subtype C protease". United Kingdom. doi:10.1107/S174430910701161X.
@article{osti_22360313,
title = {Expression, purification and preliminary X-ray crystallographic studies of the human immunodeficiency virus 1 subtype C protease},
author = {Coman, Roxana M. and Robbins, Arthur and Goodenow, Maureen M. and McKenna, Robert and Dunn, Ben M., E-mail: bdunn@ufl.edu},
abstractNote = {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.},
doi = {10.1107/S174430910701161X},
journal = {Acta Crystallographica. Section F},
number = Pt 4,
volume = 63,
place = {United Kingdom},
year = {Sun Apr 01 00:00:00 EDT 2007},
month = {Sun Apr 01 00:00:00 EDT 2007}
}