4JU7

Crystal structure of hcv ns5b polymerase in complex with compound 24

Summary for 4JU7

• Entry DOI: 10.2210/pdb4ju7/pdb
• Related: 3MWV 4JTW 4JTY 4JTZ 4JU1 4JU2 4JU3 4JU4 4JU6 4JVQ 4JY0 4JY1
• Descriptor: Genome polyprotein, 2-{[(trans-4-methylcyclohexyl)carbonyl](propan-2-yl)amino}-5-phenoxybenzoic acid, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: rna-directed rna polymerase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Hepatitis C virus (HCV)
• Cellular location: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein (By similarity). 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): O92972
• Total number of polymer chains: 2
• Total formula weight: 129015.38

Authors

Coulombe, R. (deposition date: 2013-03-24, release date: 2013-11-27, Last modification date: 2023-09-20)

Primary citation

Stammers, T.A.,Coulombe, R.,Duplessis, M.,Fazal, G.,Gagnon, A.,Garneau, M.,Goulet, S.,Jakalian, A.,Laplante, S.,Rancourt, J.,Thavonekham, B.,Wernic, D.,Kukolj, G.,Beaulieu, P.L.
Anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors with sub-micromolar potency in the cell-based replicon assay.
Bioorg.Med.Chem.Lett., 23:6879-6885, 2013

PubMed Abstract: Optimization efforts on the anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors 1 and 2 resulted in the identification of multiple structural elements that contributed to improved cell culture potency. The additive effect of these elements resulted in compound 46, an inhibitor with enzymatic (IC50) and cell culture (EC50) potencies of less than 100 nanomolar.

PubMed: 24176401
DOI: 10.1016/j.bmcl.2013.09.102

Experimental method

X-RAY DIFFRACTION (2.2 Å)