1NJT
COMPLEX STRUCTURE OF HCMV PROTEASE AND A PEPTIDOMIMETIC INHIBITOR
Summary for 1NJT
| Entry DOI | 10.2210/pdb1njt/pdb |
| Related | 1NJU 1NKK 1NKM 2WPO |
| Related PRD ID | PRD_000405 |
| Descriptor | Capsid protein P40, Peptidomimetic Inhibitor, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | protease, peptidomimetic inhibitor, induced-fit, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Human herpesvirus 5 (Human cytomegalovirus) More |
| Cellular location | Protease precursor: Host cytoplasm. Assemblin: Host nucleus. Assembly protein: Host nucleus: P16753 |
| Total number of polymer chains | 8 |
| Total formula weight | 114870.23 |
| Authors | Khayat, R.,Batra, R.,Qian, C.,Halmos, T.,Bailey, M.,Tong, L. (deposition date: 2003-01-02, release date: 2003-02-11, Last modification date: 2021-10-27) |
| Primary citation | Khayat, R.,Batra, R.,Qian, C.,Halmos, T.,Bailey, M.,Tong, L. Structural and Biochemical Studies of Inhibitor Binding to Human Cytomegalovirus Protease Biochemistry, 42:885-891, 2003 Cited by PubMed Abstract: 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. PubMed: 12549906DOI: 10.1021/bi027045s PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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