2ijn
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2ijn.gif|left|200px]] | + | [[Image:2ijn.gif|left|200px]] |
| - | + | ||
| - | '''Isothiazoles as active-site inhibitors of HCV NS5B polymerase''' | + | {{Structure |
| + | |PDB= 2ijn |SIZE=350|CAPTION= <scene name='initialview01'>2ijn</scene>, resolution 2.20Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=221:(2R,3R)-3-{[3,5-BIS(TRIFLUOROMETHYL)PHENYL]AMINO}-2-CYANO-3-THIOXOPROPANAMIDE'>221</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Isothiazoles as active-site inhibitors of HCV NS5B polymerase''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2IJN is a [ | + | 2IJN 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=2IJN OCA]. |
==Reference== | ==Reference== | ||
| - | Isothiazoles as active-site inhibitors of HCV NS5B polymerase., Yan S, Appleby T, Gunic E, Shim JH, Tasu T, Kim H, Rong F, Chen H, Hamatake R, Wu JZ, Hong Z, Yao N, Bioorg Med Chem Lett. 2007 Jan 1;17(1):28-33. Epub 2006 Oct 5. PMID:[http:// | + | Isothiazoles as active-site inhibitors of HCV NS5B polymerase., Yan S, Appleby T, Gunic E, Shim JH, Tasu T, Kim H, Rong F, Chen H, Hamatake R, Wu JZ, Hong Z, Yao N, Bioorg Med Chem Lett. 2007 Jan 1;17(1):28-33. Epub 2006 Oct 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17049853 17049853] |
[[Category: Hepatitis c virus subtype 3b]] | [[Category: Hepatitis c virus subtype 3b]] | ||
[[Category: RNA-directed RNA polymerase]] | [[Category: RNA-directed RNA polymerase]] | ||
| Line 19: | Line 28: | ||
[[Category: hcv; ns5b; viral rna directed rna polymerase; rdrp; active site; covalent inhibitor]] | [[Category: hcv; ns5b; viral rna directed rna polymerase; rdrp; active site; covalent inhibitor]] | ||
| - | ''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 17:30:23 2008'' |
Revision as of 15:30, 20 March 2008
| |||||||
| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | RNA-directed RNA polymerase, with EC number 2.7.7.48 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Isothiazoles as active-site inhibitors of HCV NS5B polymerase
Overview
Isothiazole analogs were discovered as a novel class of active-site inhibitors of HCV NS5B polymerase. The best compound has an IC(50) of 200 nM and EC(50) of 100 nM, which is a significant improvement over the starting inhibitor (1). The X-ray complex structure of 1 with HCV NS5B was obtained at a resolution of 2.2A, revealing that the inhibitor is covalently linked with Cys 366 of the 'primer-grip'. Furthermore, it makes considerable contacts with the C-terminus, beta-loop, and more importantly, to the active-site of the enzyme. The uniqueness of this binding mode offers a new insight for the rational design of novel inhibitors for HCV NS5B polymerase.
About this Structure
2IJN is a Single protein structure of sequence from Hepatitis c virus subtype 3b. Full crystallographic information is available from OCA.
Reference
Isothiazoles as active-site inhibitors of HCV NS5B polymerase., Yan S, Appleby T, Gunic E, Shim JH, Tasu T, Kim H, Rong F, Chen H, Hamatake R, Wu JZ, Hong Z, Yao N, Bioorg Med Chem Lett. 2007 Jan 1;17(1):28-33. Epub 2006 Oct 5. PMID:17049853
Page seeded by OCA on Thu Mar 20 17:30:23 2008
