2HAI

Crystal structure of HCV NS5B RNA polymerase in complex with novel class of dihydropyrone-containing inhibitor.

Summary for 2HAI

• Entry DOI: 10.2210/pdb2hai/pdb
• Related: 1OS5
• Descriptor: HEPATITIS C VIRUS NS5B RNA POLYMERASE, (6S)-6-CYCLOPENTYL-6-[2-(3-FLUORO-4-ISOPROPOXYPHENYL)ETHYL]-4-HYDROXY-5,6-DIHYDRO-2H-PYRAN-2-ONE (3 entities in total)
• Functional Keywords: hcv rna polymerase, transferase
• Biological source: Hepatitis C virus
• Cellular location: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein. Core protein p19: Virion (By similarity). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): P26663
• Total number of polymer chains: 1
• Total formula weight: 64633.01

Authors

Li, H.,Love, R.L. (deposition date: 2006-06-12, release date: 2006-09-05, Last modification date: 2024-10-30)

Primary citation

Li, H.,Tatlock, J.,Linton, A.,Gonzalez, J.,Borchardt, A.,Dragovich, P.,Jewell, T.,Prins, T.,Zhou, R.,Blazel, J.,Parge, H.,Love, R.,Hickey, M.,Doan, C.,Shi, S.,Duggal, R.,Lewis, C.,Fuhrman, S.
Identification and structure-based optimization of novel dihydropyrones as potent HCV RNA polymerase inhibitors.
Bioorg.Med.Chem.Lett., 16:4834-4838, 2006

PubMed Abstract: A novel class of non-nucleoside HCV NS5B polymerase inhibitors has been identified from screening. A co-crystal structure revealed an allosteric binding site in the protein that required a unique conformational change to accommodate inhibitor binding. Herein we report the structure-activity relationships (SARs) of this novel class of dihydropyrone-containing compounds that show potent inhibitory activities against the HCV RNA polymerase in biochemical assays.

PubMed: 16824756
DOI: 10.1016/j.bmcl.2006.06.065

Experimental method

X-RAY DIFFRACTION (1.58 Å)