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 (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(1), with mean unit-cell parameters a = 46.7 (+/-0.1), b = 59.8 (+/-0.3), c = 87.0 (+/-0.4) A, beta = 95.2 (+/-0.5) degrees. The crystals of both complexes have been shown to diffract X-rays to 2.3 A resolution. The diffraction data for the subtype C PR complexes with IDV and NFV were subsequently processed and reduced, with overall R(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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Roxana M
authors.initials: RM
authors.lastname: Coman
authors.forename: Arthur
authors.initials: A
authors.lastname: Robbins
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Goodenow
authors.forename: Robert
authors.initials: R
authors.lastname: McKenna
authors.forename: Ben M
authors.initials: BM
authors.lastname: Dunn
mesh_terms: D003460:Crystallization; D018360:Crystallography, X-Ray; D016333:HIV Protease / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification
chemical_list: D011994:Recombinant Proteins; D016333:HIV Protease