1jq7
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HCMV protease dimer-interface mutant, S225Y complexed to Inhibitor BILC 408
OverviewOverview
Biochemical studies indicate that dimerization is required for the, catalytic activity of herpesvirus proteases, whereas structural studies, show a complete active site in each monomer, away from the dimer, interface. Here we report kinetic, biophysical and crystallographic, characterizations of structure-based mutants in the dimer interface of, human cytomegalovirus (HCMV) protease. Such mutations can produce a, 1,700-fold reduction in the kcat while having minimal effects on the K(m)., Dimer stability is not affected by these mutations, suggesting that, dimerization itself is insufficient for activity. There are large changes, in monomer conformation and dimer organization of the apo S225Y mutant, enzyme. However, binding of an activated peptidomimetic inhibitor induced, a conformation remarkably similar to the wild type protease. Our studies, suggest that appropriate dimer formation may be required to indirectly, stabilize the protease oxyanion hole, revealing a novel mechanism for, dimerization to regulate enzyme activity.
About this StructureAbout this Structure
1JQ7 is a Single protein structure of sequence from Human herpesvirus 5 with BAS as ligand. Active as Assemblin, with EC number 3.4.21.97 Full crystallographic information is available from OCA.
ReferenceReference
Molecular mechanism for dimerization to regulate the catalytic activity of human cytomegalovirus protease., Batra R, Khayat R, Tong L, Nat Struct Biol. 2001 Sep;8(9):810-7. PMID:11524687
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