2HWI

HCV NS5B allosteric inhibitor complex

Summary for 2HWI

• Entry DOI: 10.2210/pdb2hwi/pdb
• Descriptor: RNA-directed RNA polymerase (NS5B) (p68), (2S)-({(5Z)-5-[(5-ETHYL-2-FURYL)METHYLENE]-4-OXO-4,5-DIHYDRO-1,3-THIAZOL-2-YL}AMINO)(4-FLUOROPHENYL)ACETIC ACID (3 entities in total)
• Functional Keywords: hcv, ns5b, viral rna-directed rna polymerase, rdrp, allosteric inhibitor, hcv inhibitor complex, transferase
• 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: 128775.42

Authors

Yao, N. (deposition date: 2006-08-01, release date: 2006-11-07, Last modification date: 2023-08-30)

Primary citation

Yan, S.,Appleby, T.,Larson, G.,Wu, J.Z.,Hamatake, R.,Hong, Z.,Yao, N.
Structure-based design of a novel thiazolone scaffold as HCV NS5B polymerase allosteric inhibitors.
Bioorg.Med.Chem.Lett., 16:5888-5891, 2006

PubMed Abstract: A structure-based approach was performed to design a novel thiazolone scaffold as HCV NS5B inhibitors. A focused library was designed and docked by GOLD. One of the top-scored molecules was synthesized and shown to have similar potency to the initial hit. The X-ray complex structure was determined and validated our design rationale.

PubMed: 16934455
DOI: 10.1016/j.bmcl.2006.08.056

Experimental method

X-RAY DIFFRACTION (2 Å)