3BSA

Crystal Structure of HCV NS5B Polymerase with a Novel Pyridazinone Inhibitor

Summary for 3BSA

• Entry DOI: 10.2210/pdb3bsa/pdb
• Related: 3BR9 3BSC
• Descriptor: RNA-directed RNA polymerase, 2-({3-[5-hydroxy-2-(3-methylbutyl)-3-oxo-6-(1,3-thiazol-5-yl)-2,3-dihydropyridazin-4-yl]-1,1-dioxido-2H-1,2,4-benzothia diazin-7-yl}oxy)acetamide (3 entities in total)
• Functional Keywords: protein-ligand complex, rna replication, rna-binding, rna-directed rna polymerase, transcription, transcription regulation, transferase, transmembrane, viral nucleoprotein
• 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: 129728.61

Authors

Han, Q.,Showalter, R.E.,Zhao, Q.,Kissinger, C.R. (deposition date: 2007-12-23, release date: 2008-12-23, Last modification date: 2024-04-03)

Primary citation

Zhou, Y.,Webber, S.E.,Murphy, D.E.,Li, L.S.,Dragovich, P.S.,Tran, C.V.,Sun, Z.,Ruebsam, F.,Shah, A.M.,Tsan, M.,Showalter, R.E.,Patel, R.,Li, B.,Zhao, Q.,Han, Q.,Hermann, T.,Kissinger, C.R.,Lebrun, L.,Sergeeva, M.V.,Kirkovsky, L.
Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda6-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 1: exploration of 7'-substitution of benzothiadiazine.
Bioorg.Med.Chem.Lett., 18:1413-1418, 2008

PubMed Abstract: 5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. The synthesis, structure-activity relationships (SAR), metabolic stability, and structure-based design approach for this new class of compounds are discussed.

PubMed: 18242088
DOI: 10.1016/j.bmcl.2008.01.007

Experimental method

X-RAY DIFFRACTION (2.3 Å)