Crystal structure of a tethered dimer of HIV-1 proteinase complexed with an inhibitor
- 1 August 1994
- journal article
- research article
- Published by Springer Nature in Nature Structural & Molecular Biology
- Vol. 1 (8) , 552-556
- https://doi.org/10.1038/nsb0894-552
Abstract
HIV-1 proteinase (HIV PR) is a dimeric enzyme composed of two identical polypeptide chains that associate with twofold symmetry. We have determined to 1.8 A the crystal structure of a covalently tethered dimer of HIV PR. The tethered dimer:inhibitor complex is identical in nearly every respect to the complex of the same inhibitor with the wild type dimeric molecule, except for the linker region. Our results suggest that the tethered dimer may be a useful surrogate enzyme for studying the effects of single site mutations on substrate and inhibitor binding as well as on enzyme asymmetry, and for simulating independent mutational drift of the two domains which has been proposed to have led to the evolution of modern day, single-chain aspartic proteinases.Keywords
This publication has 12 references indexed in Scilit:
- Influence of stereochemistry on activity and binding modes for C2 symmetry-based diol inhibitors of HIV-1 proteaseJournal of the American Chemical Society, 1994
- In vitro isolation and identification of human immunodeficiency virus (HIV) variants with reduced sensitivity to C-2 symmetrical inhibitors of HIV type 1 protease.Proceedings of the National Academy of Sciences, 1993
- Design and structure of symmetry-based inhibitors of HIV-1 proteasePerspectives in Drug Discovery and Design, 1993
- STRUCTURE-BASED INHIBITORS OF HIV-1 PROTEASEAnnual Review of Biochemistry, 1993
- Inhibitors of HIV-1 ProteaseJournal of Enzyme Inhibition, 1992
- HIV protease: a novel chemotherapeutic target for AIDSJournal of Medicinal Chemistry, 1991
- Structural and evolutionary relationships between retroviral and eukaryotic aspartic proteinasesBiochemistry, 1991
- Human immunodeficiency virus proteinase dimer as component of the viral polyprotein prevents particle assembly and viral infectivity.Proceedings of the National Academy of Sciences, 1991
- Chapter 15. HIV Protease InhibitorsPublished by Elsevier ,1991
- Stability and activity of human immunodeficiency virus protease: comparison of the natural dimer with a homologous, single-chain tethered dimer.Proceedings of the National Academy of Sciences, 1990