Rous sarcoma virus retropepsin and avian myeloblastosis virus retropepsin

This chapter covers the structural chemistry and the biological aspects of Rous Sarcoma Virus (RSV) retropepsin and Avian Myeloblastosis Virus (AMV) retropepsin. The RSV, identified by Peyton Rous as a tumor-causing agent in 1911, contains an RNA genome that encodes three genes required for replication. These genes, gag, pol and env, are translated to yield three large precursor polyproteins: Gag, Gag-Pol and Env. During virus maturation, Gag and Gag-Pol are cleaved into eight different mature proteins by a viral specific protease. The AMV retropepsin and RSV retropepsin differ by only two amino acid residues, and are biochemically indistinguishable. Functionally active RSV/AMV protease is a symmetric homodimer with two identical subunits of 124 amino acids each. There is one high-resolution crystal structure of the native enzyme without a substrate or a inhibitor. The active site and the substrate binding site are formed by an obvious cleft at the dimer interface.