5G48

H.pylori Beta clamp in complex with Diflunisal

Summary for 5G48

• Entry DOI: 10.2210/pdb5g48/pdb
• Descriptor: DNA POLYMERASE III SUBUNIT BETA, 5-(2,4-DIFLUOROPHENYL)-2-HYDROXY-BENZOIC ACID (3 entities in total)
• Functional Keywords: transferase, dna sliding clamp, processivity promoting factor
• Biological source: HELICOBACTER PYLORI
• Cellular location: Cytoplasm : O25242
• Total number of polymer chains: 2
• Total formula weight: 84977.28

Authors

Pandey, P.,Gourinath, S. (deposition date: 2016-05-06, release date: 2017-06-21, Last modification date: 2024-01-10)

Primary citation

Pandey, P.,Verma, V.,Gautam, G.,Kumari, N.,Dhar, S.K.,Gourinath, S.
Targeting the beta-clamp in Helicobacter pylori with FDA-approved drugs reveals micromolar inhibition by diflunisal.
FEBS Lett., 591:2311-2322, 2017

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.

PubMed: 28656718
DOI: 10.1002/1873-3468.12734

Experimental method

X-RAY DIFFRACTION (2.28 Å)