3CDE

Crystal structure of HCV NS5B polymerase with a novel Pyridazinone inhibitor

Summary for 3CDE

• Entry DOI: 10.2210/pdb3cde/pdb
• Related: 3BR9 3BSA 3BSC
• Descriptor: RNA-directed RNA polymerase, N-{3-[5-hydroxy-2-(3-methylbutyl)-3-oxo-6-thiophen-2-yl-2,3-dihydropyridazin-4-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, atp-binding, host-virus interaction, hydrolase, metal-binding, nucleotide-binding, nucleotidyltransferase, ribonucleoprotein, transcription, transcription regulation, transferase, viral nucleoprotein, virion
• 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: 2
• Total formula weight: 129766.74

Authors

Zhao, Q.,Showalter, R.E.,Han, Q.,Kissinger, C.R. (deposition date: 2008-02-26, release date: 2009-03-03, Last modification date: 2024-04-03)

• Primary citation: Li, L.S.,Zhou, Y.,Murphy, D.E.,Stankovic, N.,Zhao, J.,Dragovich, P.S.,Bertolini, T.,Sun, Z.,Ayida, B.,Tran, C.V.,Ruebsam, F.,Webber, S.E.,Shah, A.M.,Tsan, M.,Showalter, R.E.,Patel, R.,Lebrun, L.A.,Bartkowski, D.M.,Nolan, T.G.,Norris, D.A.,Kamran, R.,Brooks, J.,Sergeeva, M.V.,Kirkovsky, L.,Zhao, Q.,Kissinger, C.R.; Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 3: Further optimization of the 2-, 6-, and 7'-substituents and initial pharmacokinetic assessments.; Bioorg.Med.Chem.Lett., 18:3446-3455, 2008; PubMed: 18457949; DOI: 10.1016/j.bmcl.2008.02.072

Experimental method

X-RAY DIFFRACTION (2.1 Å)