3H2L

Crystal structure of HCV NS5B polymerase in complex with a novel bicyclic dihydro-pyridinone inhibitor

Summary for 3H2L

• Entry DOI: 10.2210/pdb3h2l/pdb
• Descriptor: NS5B polymerase, N-{3-[(4aR,7aS)-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-cyclopenta[b]pyridin-3-yl]-1,1-dioxido-2H-1,2,4-benzothiadiazin-7-yl}methanesulfonamide (3 entities in total)
• Functional Keywords: protein-ligand complex, hepatitis c, rna replication, rna-binding, rna-directed rna polymerase, transferase, acetylation, apoptosis, atp-binding
• Biological source: Hepatitis C virus (isolate BK) (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: 129760.64

Authors

Han, Q.,Showalter, R.E.,Zhou, Q.,Kissinger, C.R. (deposition date: 2009-04-14, release date: 2009-12-08, Last modification date: 2024-04-03)

• Primary citation: Ruebsam, F.,Murphy, D.E.,Tran, C.V.,Li, L.S.,Zhao, J.,Dragovich, P.S.,McGuire, H.M.,Xiang, A.X.,Sun, Z.,Ayida, B.K.,Blazel, J.K.,Kim, S.H.,Zhou, Y.,Han, Q.,Kissinger, C.R.,Webber, S.E.,Showalter, R.E.,Shah, A.M.,Tsan, M.,Patel, R.A.,Thompson, P.A.,Lebrun, L.A.,Hou, H.J.,Kamran, R.,Sergeeva, M.V.,Bartkowski, D.M.,Nolan, T.G.,Norris, D.A.,Khandurina, J.,Brooks, J.,Okamoto, E.,Kirkovsky, L.; Discovery of tricyclic 5,6-dihydro-1H-pyridin-2-ones as novel, potent, and orally bioavailable inhibitors of HCV NS5B polymerase.; Bioorg.Med.Chem.Lett., 19:6404-6412, 2009; PubMed: 19818610; DOI: 10.1016/j.bmcl.2009.09.045

Experimental method

X-RAY DIFFRACTION (1.9 Å)