Structural highlights
Function
[DPO3B_HELPY] DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. This DNA polymerase also exhibits 3' to 5' exonuclease activity. The beta chain is required for initiation of replication once it is clamped onto DNA, it slides freely (bidirectional and ATP-independent) along duplex DNA (By similarity).
Publication Abstract from PubMed
The beta-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 beta-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 beta-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 beta-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.
Targeting the beta-clamp in Helicobacter pylori with FDA-approved drugs reveals micromolar inhibition by diflunisal.,Pandey P, Verma V, Gautam G, Kumari N, Dhar SK, Gourinath S FEBS Lett. 2017 Aug;591(15):2311-2322. doi: 10.1002/1873-3468.12734. Epub 2017, Jul 26. PMID:28656718[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pandey P, Verma V, Gautam G, Kumari N, Dhar SK, Gourinath S. Targeting the beta-clamp in Helicobacter pylori with FDA-approved drugs reveals micromolar inhibition by diflunisal. FEBS Lett. 2017 Aug;591(15):2311-2322. doi: 10.1002/1873-3468.12734. Epub 2017, Jul 26. PMID:28656718 doi:http://dx.doi.org/10.1002/1873-3468.12734
