4EO8

HCV NS5B polymerase inhibitors: Tri-substituted acylhydrazines as tertiary amide bioisosteres

Summary for 4EO8

• Entry DOI: 10.2210/pdb4eo8/pdb
• Related: 4EO6
• Descriptor: RNA-directed RNA polymerase, 5-(3,3-dimethylbut-1-yn-1-yl)-3-{2,2-dimethyl-1-[(trans-4-methylcyclohexyl)carbonyl]hydrazinyl}thiophene-2-carboxylic acid (3 entities in total)
• Functional Keywords: hcv, ns5b, rna, rna polymerase, polymerase inhibitor, thumb site 2 inhibitor, rna-dependent rna polymerase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Hepatitis C virus (isolate BK) (HCV)
• 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: 2
• Total formula weight: 129070.12

Authors

Appleby, T.C.,Canales, E.,Watkins, W.J. (deposition date: 2012-04-13, release date: 2012-06-27, Last modification date: 2023-09-13)

• Primary citation: Canales, E.,Carlson, J.S.,Appleby, T.,Fenaux, M.,Lee, J.,Tian, Y.,Tirunagari, N.,Wong, M.,Watkins, W.J.; Tri-substituted acylhydrazines as tertiary amide bioisosteres: HCV NS5B polymerase inhibitors.; Bioorg.Med.Chem.Lett., 22:4288-4292, 2012; PubMed: 22664130; DOI: 10.1016/j.bmcl.2012.05.025

Experimental method

X-RAY DIFFRACTION (1.798 Å)