5G48

Targeting the beta-clamp in Helicobacter pylori with FDA-approved drugs reveals micromolar inhibition by diflunisal.

(2017) FEBS Lett 591: 2311-2322

• PubMed: 28656718 Search on PubMed
• DOI: https://doi.org/10.1002/1873-3468.12734
• Primary Citation of Related Structures:  
  5G48


• PubMed Abstract: 
  

  The β-clamp is the processivity-promoting factor for most of the enzymes in prokaryotic DNA replication; hence, it is a crucial drug target. In the present study, we investigated the β-clamp from Helicobacter pylori, aiming to seek potential drug molecules against this gastric-cancer-causing bacterium. An in?silico screening of Food and Drug Administration (FDA) approved drugs against the H.?pylori β-clamp, followed by its in?vitro inhibition using a surface competition approach, yielded the drug diflunisal as a positive initial hit. Diflunisal inhibits the growth of H.?pylori in the micromolar range. We determined the structure of diflunisal in complex with the β-clamp to show that the drug binds at subsite I, which is a protein-protein interaction site. Successful identification of FDA-approved molecules against H.?pylori may lead to better and faster drug development.

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Organizational Affiliation: 

School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.