4IH7

Hepatitis C Virus polymerase NS5B (BK) with fragment-based compounds

Summary for 4IH7

• Entry DOI: 10.2210/pdb4ih7/pdb
• Related: 4IH5 4IH6
• Descriptor: RNA-directed RNA polymerase, ZINC ION, 3-(3-tert-butylphenyl)pyridin-2(1H)-one, ... (4 entities in total)
• Functional Keywords: fragment based drug design, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Hepatitis C virus (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: 127294.86

Authors

Harris, S.F.,Wong, A. (deposition date: 2012-12-18, release date: 2013-07-03, Last modification date: 2024-10-09)

Primary citation

Talamas, F.X.,Ao-Ieong, G.,Brameld, K.A.,Chin, E.,de Vicente, J.,Dunn, J.P.,Ghate, M.,Giannetti, A.M.,Harris, S.F.,Labadie, S.S.,Leveque, V.,Li, J.,Lui, A.S.,McCaleb, K.L.,Najera, I.,Schoenfeld, R.C.,Wang, B.,Wong, A.
De novo fragment design: a medicinal chemistry approach to fragment-based lead generation.
J.Med.Chem., 56:3115-3119, 2013

PubMed Abstract: The use of fragments with low binding affinity for their targets as starting points has received much attention recently. Screening of fragment libraries has been the most common method to find attractive starting points. Herein, we describe a unique, alternative approach to generating fragment leads. A binding model was developed and a set of guidelines were then selected to use this model to design fragments, enabling our discovery of a novel fragment with high LE.

PubMed: 23509929
DOI: 10.1021/jm4002605

Experimental method

X-RAY DIFFRACTION (2.3 Å)