1dy8
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The hepatitis C virus NS3 protein contains a serine protease domain with a | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Viruses]] | [[Category: Viruses]] | ||
[[Category: Colarusso, S.]] | [[Category: Colarusso, S.]] | ||
| - | [[Category: Francesco, R | + | [[Category: Francesco, R De.]] |
| - | [[Category: Marco, S | + | [[Category: Marco, S Di.]] |
| - | [[Category: Matassa, V | + | [[Category: Matassa, V G.]] |
[[Category: Narjes, F.]] | [[Category: Narjes, F.]] | ||
[[Category: Rizzi, M.]] | [[Category: Rizzi, M.]] | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:21:46 2008'' |
Revision as of 10:21, 21 February 2008
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INHIBITION OF THE HEPATITIS C VIRUS NS3/4A PROTEASE. THE CRYSTAL STRUCTURES OF TWO PROTEASE-INHIBITOR COMPLEXES (INHIBITOR II)
Overview
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.
About this Structure
1DY8 is a Single protein structure of sequence from Viruses. Known structural/functional Sites: and . Full crystallographic information is available from OCA.
Reference
Inhibition of the hepatitis C virus NS3/4A protease. The crystal structures of two protease-inhibitor complexes., Di Marco S, Rizzi M, Volpari C, Walsh MA, Narjes F, Colarusso S, De Francesco R, Matassa VG, Sollazzo M, J Biol Chem. 2000 Mar 10;275(10):7152-7. PMID:10702283
Page seeded by OCA on Thu Feb 21 12:21:46 2008
