1DY9

Inhibition of the Hepatitis C Virus NS3/4A Protease. The Crystal Structures of Two Protease-Inhibitor Complexes (inhibitor I)

1DY9 の概要

• エントリーDOI: 10.2210/pdb1dy9/pdb
• 関連するPDBエントリー: 1DXP 1DY8 1JXP
• 関連するBIRD辞書のPRD_ID: PRD_000426
• 分子名称: PROTEASE/HELICASE NS3 (P70), NONSTRUCTURAL PROTEIN NS4A (P4), N-(tert-butoxycarbonyl)-L-alpha-glutamyl-N-[(1R)-1-(carboxycarbonyl)-3,3-difluoropropyl]-L-leucinamide, ... (5 entities in total)
• 機能のキーワード: serine protease, ns3, ns4a, hepatitis c virus, protease inhibition, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: HEPATITIS C VIRUS (ISOLATE TAIWAN); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 43955.71

構造登録者

Di Marco, S.,Rizzi, M.,Volpari, C.,Walsh, M.,Narjes, F.,Colarusso, S.,De Francesco, R.,Matassa, V.G.,Sollazzo, M. (登録日: 2000-01-31, 公開日: 2001-01-28, 最終更新日: 2023-12-06)

主引用文献

Di Marco, S.,Rizzi, M.,Volpari, C.,Walsh, M.,Narjes, F.,Colarusso, S.,De Francesco, R.,Matassa, V.G.,Sollazzo, M.
Inhibition of the Hepatitis C Virus Ns3/4A Protease the Crystal Structures of Two Protease-Inhibitor Complexes
J.Biol.Chem., 275:7152-, 2000

PubMed Abstract: The hepatitis C virus NS3 protein contains a serine protease domain with a chymotrypsin-like fold, which is a target for development of therapeutics. We report the crystal structures of this domain complexed with NS4A cofactor and with two potent, reversible covalent inhibitors spanning the P1-P4 residues. Both inhibitors bind in an extended backbone conformation, forming an anti-parallel beta-sheet with one enzyme beta-strand. The P1 residue contributes most to the binding energy, whereas P2-P4 side chains are partially solvent exposed. The structures do not show notable rearrangements of the active site upon inhibitor binding. These results are significant for the development of antivirals.

PubMed: 10702283
DOI: 10.1074/JBC.275.10.7152

実験手法

X-RAY DIFFRACTION (2.1 Å)