A Conserved Pocket in the Dengue Virus Polymerase Identified through Fragment-based Screening.

@article{Noble2016ACP,
  title={A Conserved Pocket in the Dengue Virus Polymerase Identified through Fragment-based Screening.},
  author={Christian Guy Noble and Siew Pheng Lim and Rishi Arora and Fumiaki Yokokawa and Shahul Nilar and Cheah Chen Seh and S Kirk Wright and Timothy E. Benson and Paul W. Smith and Pei-Yong Shi},
  journal={The Journal of biological chemistry},
  year={2016},
  volume={291 16},
  pages={8541-8}
}
We performed a fragment screen on the dengue virus serotype 3 RNA-dependent RNA polymerase using x-ray crystallography. A screen of 1,400 fragments in pools of eight identified a single hit that bound in a novel pocket in the protein. This pocket is located in the polymerase palm subdomain and conserved across the four serotypes of dengue virus. The compound binds to the polymerase in solution as evidenced by surface plasmon resonance and isothermal titration calorimetry analyses. Related… CONTINUE READING