1DY8

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

Summary for 1DY8

• Entry DOI: 10.2210/pdb1dy8/pdb
• Related: 1DXP 1DY9 1JXP
• Related PRD ID: PRD_000271
• Descriptor: PROTEASE/HELICASE NS3 (P70), NONSTRUCTURAL PROTEIN NS4A (P4), N-[(benzyloxy)carbonyl]-L-isoleucyl-N-[(1R)-1-(carboxycarbonyl)-3,3-difluoropropyl]-L-leucinamide, ... (4 entities in total)
• Functional Keywords: serine protease, protease inhibition, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: HEPATITIS C VIRUS (ISOLATE TAIWAN); More
• Total number of polymer chains: 4
• Total formula weight: 43926.42

Authors

Di Marco, S.,Rizzi, M.,Volpari, C.,Walsh, M.,Narjes, F.,Colarusso, S.,De Francesco, R.,Matassa, V.G.,Sollazzo, M. (deposition date: 2000-01-31, release date: 2001-01-28, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)