3CO9

Crystal structure of HCV NS5B polymerase with a novel pyridazinone inhibitor

Summary for 3CO9

• Entry DOI: 10.2210/pdb3co9/pdb
• Related: 3BR9 3BSA 3BSC
• Descriptor: RNA-directed RNA polymerase, N-{3-[4-hydroxy-1-(3-methylbutyl)-2-oxo-1,2-dihydropyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxido-2H-1,2,4-benzothiadiazin-7 -yl}methanesulfonamide (3 entities in total)
• Functional Keywords: protein-ligand complex, nucleotide binding, nucleotidyltransferase, ribonucleoprotein, rna replication, rna-binding, rna-directed rna polymerase, transcription, transferase, antiviral, hydrolase, nucleotide-binding
• 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: 129678.59

Authors

Han, Q.,Showalter, R.E.,Zhao, Q.,Kissinger, C.R. (deposition date: 2008-03-27, release date: 2009-02-10, Last modification date: 2024-04-03)

• Primary citation: Ruebsam, F.,Webber, S.E.,Tran, M.T.,Tran, C.V.,Murphy, D.E.,Zhao, J.,Dragovich, P.S.,Kim, S.H.,Li, L.S.,Zhou, Y.,Han, Q.,Kissinger, C.R.,Showalter, R.E.,Lardy, M.,Shah, A.M.,Tsan, M.,Patel, R.,Lebrun, L.A.,Kamran, R.,Sergeeva, M.V.,Bartkowski, D.M.,Nolan, T.G.,Norris, D.A.,Kirkovsky, L.; Pyrrolo[1,2-b]pyridazin-2-ones as potent inhibitors of HCV NS5B polymerase.; Bioorg.Med.Chem.Lett., 18:3616-3621, 2008; PubMed: 18487044; DOI: 10.1016/j.bmcl.2008.04.066

Experimental method

X-RAY DIFFRACTION (2.1 Å)