3E51

Crystal structure of HCV NS5B polymerase with a novel pyridazinone inhibitor

Summary for 3E51

• Entry DOI: 10.2210/pdb3e51/pdb
• Related: 3BR9 3BSA 3BSC 3CDE 3CO9 3CVK 3CWJ
• Descriptor: RNA-directed RNA polymerase, N-{3-[5-hydroxy-2-(3-methylbutyl)-3-oxo-6-pyrrolidin-1-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-directed rna polymerase, nucleotidyltransferase, nucleotide-binding, transcription, transferase
• 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: 129740.70

Authors

Han, Q.,Showalter, R.E.,Zhao, Q.,Kissinger, C.R. (deposition date: 2008-08-12, release date: 2009-08-18, Last modification date: 2024-04-03)

• Primary citation: Dragovich, P.S.,Blazel, J.K.,Ellis, D.A.,Han, Q.,Kamran, R.,Kissinger, C.R.,LeBrun, L.A.,Li, L.S.,Murphy, D.E.,Noble, M.,Patel, R.A.,Ruebsam, F.,Sergeeva, M.V.,Shah, A.M.,Showalter, R.E.,Tran, C.V.,Tsan, M.,Webber, S.E.,Kirkovsky, L.,Zhou, Y.; 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 5: Exploration of pyridazinones containing 6-amino-substituents.; Bioorg.Med.Chem.Lett., 18:5635-5639, 2008; PubMed: 18796353; DOI: 10.1016/j.bmcl.2008.08.094

Experimental method

X-RAY DIFFRACTION (1.9 Å)