2DXS

Crystal structure of HCV NS5B RNA polymerase complexed with a tetracyclic inhibitor

Summary for 2DXS

• Entry DOI: 10.2210/pdb2dxs/pdb
• Related: 1QUV
• Descriptor: Genome polyprotein, N-[(13-CYCLOHEXYL-6,7-DIHYDROINDOLO[1,2-D][1,4]BENZOXAZEPIN-10-YL)CARBONYL]-2-METHYL-L-ALANINE (3 entities in total)
• Functional Keywords: hcv, ns5b, rna polymerase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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: 123607.73

Authors

Adachi, T.,Tsuruha, J.,Doi, S.,Murase, K.,Ikegashira, K.,Watanabe, S.,Uehara, K.,Orita, T.,Nomura, A.,Kamada, M. (deposition date: 2006-08-30, release date: 2006-12-26, Last modification date: 2023-10-25)

Primary citation

Ikegashira, K.,Oka, T.,Hirashima, S.,Noji, S.,Yamanaka, H.,Hara, Y.,Adachi, T.,Tsuruha, J.,Doi, S.,Hase, Y.,Noguchi, T.,Ando, I.,Ogura, N.,Ikeda, S.,Hashimoto, H.
Discovery of Conformationally Constrained Tetracyclic Compounds as Potent Hepatitis C Virus NS5B RNA Polymerase Inhibitors
J.Med.Chem., 49:6950-6953, 2006

PubMed Abstract: We report a new series of hepatitis C virus NS5B RNA polymerase inhibitors containing a conformationally constrained tetracyclic scaffold. SAR studies led to the identification of 6,7-dihydro-5H-benzo[5,6][1,4]diazepino[7,1-a]indoles (19 and 20) bearing a basic pendent group with high biochemical and cellular potencies. These compounds displayed a very small shift in cellular potency when the replicon assay was performed in the presence of human serum albumin.

PubMed: 17125247
DOI: 10.1021/jm0610245

Experimental method

X-RAY DIFFRACTION (2.2 Å)