8J3S

Complex structure of human cytomegalovirus protease and a macrocyclic peptide ligand

8J3S の概要

• エントリーDOI: 10.2210/pdb8j3s/pdb
• 分子名称: Assemblin, PHE-ILE-THR-GLY-HIS-TYR-TRP-VAL-ARG-PHE-LEU-PRO-CYS-GLY (3 entities in total)
• 機能のキーワード: protease, hydrolase
• 由来する生物種: Human betaherpesvirus 5; 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 121619.69

構造登録者

Yoshida, S.,Sako, Y.,Nikaido, E.,Ueda, T.,Kozono, I.,Ichihashi, Y.,Nakahashi, A.,Onishi, M.,Yamatsu, Y.,Kato, T.,Nishikawa, J.,Tachibana, Y. (登録日: 2023-04-18, 公開日: 2023-11-08, 最終更新日: 2023-11-29)

主引用文献

Yoshida, S.,Sako, Y.,Nikaido, E.,Ueda, T.,Kozono, I.,Ichihashi, Y.,Nakahashi, A.,Onishi, M.,Yamatsu, Y.,Kato, T.,Nishikawa, J.,Tachibana, Y.
Peptide-to-Small Molecule: Discovery of Non-Covalent, Active-Site Inhibitors of beta-Herpesvirus Proteases.
Acs Med.Chem.Lett., 14:1558-1566, 2023

PubMed Abstract: Viral proteases, the key enzymes that regulate viral replication and assembly, are promising targets for antiviral drug discovery. Herpesvirus proteases are enzymes with no crystallographically confirmed noncovalent active-site binders, owing to their shallow and polar substrate-binding pockets. Here, we applied our previously reported "Peptide-to-Small Molecule" strategy to generate novel inhibitors of β-herpesvirus proteases. Rapid selection with a display technology was used to identify macrocyclic peptide bound to the active site of human cytomegalovirus protease (HCMV) with high affinity, and pharmacophore queries were defined based on the results of subsequent intermolecular interaction analyses. Membrane-permeable small molecule , designed according to this hypothesis, exhibited enzyme inhibitory activity (IC = 10 to 10 M) against β-herpesvirus proteases, and the design concept was proved by X-ray cocrystal analysis.

PubMed: 37974946
DOI: 10.1021/acsmedchemlett.3c00359

実験手法

X-RAY DIFFRACTION (3.09 Å)