3IGV

Crystal structure of HCV NS5B polymerase with a novel monocyclic dihydro-pyridinone inhibitor

Summary for 3IGV

• Entry DOI: 10.2210/pdb3igv/pdb
• Related: 3GYN
• Descriptor: RNA-DIRECTED RNA POLYMERASE, N-{3-[(6S)-6-ethyl-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-2H-1,2,4-benzothiadiazin-7-yl}methanesulfonamide (3 entities in total)
• Functional Keywords: protein-ligand complex, rna replication, rna-binding, rna-directed rna polymerase, hydrolase, antiviral, metal binding, nucleotide-binding, nucleotidyltransferase, transferase, atp-binding, disulfide bond, host-virus interaction, metal-binding, multifunctional enzyme, nucleus, transcription, transcription regulation, viral nucleoprotein, virion, zinc
• Biological source: Hepatitis C virus (isolate BK)
• 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: 129736.62

Authors

Zhao, Q.,Showalter, R.E.,Han, Q.,Kissinger, C.R. (deposition date: 2009-07-28, release date: 2009-12-08, Last modification date: 2024-04-03)

• Primary citation: Ellis, D.A.,Blazel, J.K.,Tran, C.V.,Ruebsam, F.,Murphy, D.E.,Li, L.S.,Zhao, J.,Zhou, Y.,McGuire, H.M.,Xiang, A.X.,Webber, S.E.,Zhao, Q.,Han, Q.,Kissinger, C.R.,Lardy, M.,Gobbi, A.,Showalter, R.E.,Shah, A.M.,Tsan, M.,Patel, R.A.,LeBrun, L.A.,Kamran, R.,Bartkowski, D.M.,Nolan, T.G.,Norris, D.A.,Sergeeva, M.V.,Kirkovsky, L.; 5,5'- and 6,6'-dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of HCV NS5B polymerase.; Bioorg.Med.Chem.Lett., 19:6047-6052, 2009; PubMed: 19796938; DOI: 10.1016/j.bmcl.2009.09.051

Experimental method

X-RAY DIFFRACTION (2.6 Å)