1NKM

Complex structure of HCMV Protease and a peptidomimetic inhibitor

1NKM の概要

• エントリーDOI: 10.2210/pdb1nkm/pdb
• 関連するPDBエントリー: 1NJT 1NJU 1NKK 2WPO
• 関連するBIRD辞書のPRD_ID: PRD_000283
• 分子名称: Assemblin, N-(6-aminohexanoyl)-3-methyl-L-valyl-3-methyl-L-valyl-N~1~-[(2S,3S)-3-hydroxy-4-oxo-4-{[(1R)-1-phenylpropyl]amino}butan-2-yl]-N~4~,N~4~-dimethyl-L-aspartamide (2 entities in total)
• 機能のキーワード: protease, peptidomimetic inhibitor, induced-fit, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human herpesvirus 5 (Human cytomegalovirus)
• 細胞内の位置: Protease precursor: Host cytoplasm. Assemblin: Host nucleus. Assembly protein: Host nucleus: P16753
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56979.03

構造登録者

Khayat, R.,Batra, R.,Qian, C.,Halmos, T.,Bailey, M.,Tong, L. (登録日: 2003-01-03, 公開日: 2003-02-11, 最終更新日: 2024-10-30)

主引用文献

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

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: 12549906
DOI: 10.1021/bi027045s

実験手法

X-RAY DIFFRACTION (2.7 Å)