1os5
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1os5.jpg|left|200px]] | + | [[Image:1os5.jpg|left|200px]] |
| - | + | ||
| - | '''Crystal structure of HCV NS5B RNA polymerase complexed with a novel non-competitive inhibitor.''' | + | {{Structure |
| + | |PDB= 1os5 |SIZE=350|CAPTION= <scene name='initialview01'>1os5</scene>, resolution 2.2Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NH1:3-(4-AMINO-2-TERT-BUTYL-5-METHYL-PHENYLSULFANYL)-6-CYCLOPENTYL-4-HYDROXY-6-[2-(4-HYDROXY-PHENYL)-ETHYL]-5,6-DIHYDRO-PYRAN-2-ONE'>NH1</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= NS5B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=42791 Hepatitis C virus subtype 3b]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of HCV NS5B RNA polymerase complexed with a novel non-competitive inhibitor.''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1OS5 is a [ | + | 1OS5 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_3b Hepatitis c virus subtype 3b]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OS5 OCA]. |
==Reference== | ==Reference== | ||
| - | Crystallographic identification of a noncompetitive inhibitor binding site on the hepatitis C virus NS5B RNA polymerase enzyme., Love RA, Parge HE, Yu X, Hickey MJ, Diehl W, Gao J, Wriggers H, Ekker A, Wang L, Thomson JA, Dragovich PS, Fuhrman SA, J Virol. 2003 Jul;77(13):7575-81. PMID:[http:// | + | Crystallographic identification of a noncompetitive inhibitor binding site on the hepatitis C virus NS5B RNA polymerase enzyme., Love RA, Parge HE, Yu X, Hickey MJ, Diehl W, Gao J, Wriggers H, Ekker A, Wang L, Thomson JA, Dragovich PS, Fuhrman SA, J Virol. 2003 Jul;77(13):7575-81. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12805457 12805457] |
[[Category: Hepatitis c virus subtype 3b]] | [[Category: Hepatitis c virus subtype 3b]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 28: | Line 37: | ||
[[Category: enzyme-inhibitor complex]] | [[Category: enzyme-inhibitor complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:14:51 2008'' |
Revision as of 11:14, 20 March 2008
| |||||||
| , resolution 2.2Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | NS5B (Hepatitis C virus subtype 3b) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of HCV NS5B RNA polymerase complexed with a novel non-competitive inhibitor.
Overview
The virus-encoded nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) is an RNA-dependent RNA polymerase and is absolutely required for replication of the virus. NS5B exhibits significant differences from cellular polymerases and therefore has become an attractive target for anti-HCV therapy. Using a high-throughput screen, we discovered a novel NS5B inhibitor that binds to the enzyme noncompetitively with respect to nucleotide substrates. Here we report the crystal structure of NS5B complexed with this small molecule inhibitor. Unexpectedly, the inhibitor is bound within a narrow cleft on the protein's surface in the "thumb" domain, about 30 A from the enzyme's catalytic center. The interaction between this inhibitor and NS5B occurs without dramatic changes to the structure of the protein, and sequence analysis suggests that the binding site is conserved across known HCV genotypes. Possible mechanisms of inhibition include perturbation of protein dynamics, interference with RNA binding, and disruption of enzyme oligomerization.
About this Structure
1OS5 is a Single protein structure of sequence from Hepatitis c virus subtype 3b. Full crystallographic information is available from OCA.
Reference
Crystallographic identification of a noncompetitive inhibitor binding site on the hepatitis C virus NS5B RNA polymerase enzyme., Love RA, Parge HE, Yu X, Hickey MJ, Diehl W, Gao J, Wriggers H, Ekker A, Wang L, Thomson JA, Dragovich PS, Fuhrman SA, J Virol. 2003 Jul;77(13):7575-81. PMID:12805457
Page seeded by OCA on Thu Mar 20 13:14:51 2008
