1njt

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spinqualitylabelsall models 1njt, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

COMPLEX STRUCTURE OF HCMV PROTEASE AND A PEPTIDOMIMETIC INHIBITOR

Overview

Herpesvirus protease is required for the life cycle of the virus and is an, attractive target for the design and development of new anti-herpes, agents. The protease belongs to a new class of serine proteases, with a, novel backbone fold and a unique Ser-His-His catalytic triad. Here we, report the crystal structures of human cytomegalovirus protease in complex, with two peptidomimetic inhibitors. The structures reveal a new, hydrogen-bonding interaction between the main chain carbonyl of the P(5), residue and the main chain amide of amino acid 137 of the protease, which, is important for the binding affinity of the inhibitor. Conformational, flexibility was observed in the S(3) pocket of the enzyme, and this is, supported by our characterization of several mutants in this pocket. One, of the structures is at 2.5 A resolution, allowing us for the first time, to locate ordered solvent molecules in the inhibitor complex. The presence, of two solvent molecules in the active site may have implications for the, design of new inhibitors against this enzyme. Favorable and stereospecific, interactions have been established in the S(1)' pocket for one of these, inhibitors.

About this Structure

1NJT is a Single protein structure of sequence from Human herpesvirus 5 with CL, ACE and CFT as ligands. Active as Assemblin, with EC number 3.4.21.97 Full crystallographic information is available from OCA.

Reference

Structural and biochemical studies of inhibitor binding to human cytomegalovirus protease., Khayat R, Batra R, Qian C, Halmos T, Bailey M, Tong L, Biochemistry. 2003 Feb 4;42(4):885-91. PMID:12549906

Page seeded by OCA on Tue Nov 20 22:19:41 2007