Human Immunodeficiency Virus type 1
Human immunodeficiency virus (HIV) infection has become a major health problem over the past few decades, despite the fact that it is a fairly non-contagious virus. One can live in close association with an HIV infected person without any fear of infection. Doing the same with a person who suffers from influenza or tuberculosis is a rather bad idea. Until not too long ago however, being infected with HIV was akin to a death sentence because the target of the virus are the T cells of the immune system, our prime defense against infections. HIV has generated intense interest in the pharmaceutical industry and lead to the discovery of several efficient drugs. In order to keep HIV at bay and to minimize the onset of drug resistance, multi-drug medications for the treatment of HIV infection are the rule. One of the early targets had been its reverse transcriptase, another target has been the viral protease. This protease is important for processing of the viral polyprotein into separate proteins and an essential step in the reproduction cycle of the virus. Inhibiting it is therefore an attractive option for HIV treatment.
The viral protease occurs as a symmetric dimer with the active site formed by the two monomers together. This gives it almost a butterfly-like shape. Shown here is the structure of this dimer together with a seven-residue long peptide. The sequence of this peptide has been based on the sequence of the substrate and chemically modified. Study of the complex allows us to analyze in detail how the viral protease interacts with the substrate and use this information to design new and better inhibitors.
Protein Data Bank (PDB)
Swain, A.L. Miller, M.M. Green, J. Rich, D.H. Schneider, J. Kent, S.B. Wlodawer, A.; "X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor."; Proc. Natl. Acad. Sci. U.S.A.; (1990) 87:8805-8809 PubMed:2247451.
author: Arno Paehler