Molecular mechanism for dimerization to regulate the catalytic activity of human cytomegalovirus protease.

摘要: Biochemical studies indicate that dimerization is required for the catalytic activity of herpesvirus proteases, whereas structural show a complete active site in each monomer, away from dimer interface. Here we report kinetic, biophysical and crystallographic characterizations structure-based mutants interface human cytomegalovirus (HCMV) protease. Such mutations can produce 1,700-fold reduction kcat while having minimal effects on Km. Dimer stability not affected by these mutations, suggesting itself insufficient activity. There are large changes monomer conformation organization apo S225Y mutant enzyme. However, binding an activated peptidomimetic inhibitor induced remarkably similar to wild type Our suggest appropriate formation may be indirectly stabilize protease oxyanion hole, revealing novel mechanism regulate enzyme