5G4Q

H.pylori Beta clamp in complex with 5-chloroisatin

Summary for 5G4Q

• Entry DOI: 10.2210/pdb5g4q/pdb
• Descriptor: DNA POLYMERASE III SUBUNIT BETA, 5-chloro-1H-indole-2,3-dione (3 entities in total)
• Functional Keywords: transferase, dna sliding clamp, processivity promoting factor
• Biological source: HELICOBACTER PYLORI
• Total number of polymer chains: 2
• Total formula weight: 84658.46

Authors

Pandey, P.,Gourinath, S. (deposition date: 2016-05-16, release date: 2017-06-21, Last modification date: 2024-01-10)

Primary citation

Pandey, P.,Verma, V.,Dhar, S.K.,Gourinath, S.
Screening of E. coli beta-clamp Inhibitors Revealed that Few Inhibit Helicobacter pylori More Effectively: Structural and Functional Characterization.
Antibiotics (Basel), 7:-, 2018

PubMed Abstract: The characteristic of interaction with various enzymes and processivity-promoting nature during DNA replication makes β-clamp an important drug target. () have several unique features in DNA replication machinery that makes it different from other microorganisms. To find out whether difference in DNA replication proteins behavior accounts for any difference in drug response when compared to , in the present study, we have tested β-clamp inhibitor molecules against β-clamp. Various approaches were used to test the binding of inhibitors to β-clamp including docking, surface competition assay, complex structure determination, as well as antimicrobial assay. Out of five shortlisted inhibitor molecules on the basis of docking score, three molecules, 5-chloroisatin, carprofen, and 3,4-difluorobenzamide were co-crystallized with β-clamp and the structures show that they bind at the protein-protein interaction site as expected. In vivo studies showed only two molecules, 5-chloroisatin, and 3,4-difluorobenzamide inhibited the growth of the pylori with MIC values in micro molar range, which is better than the inhibitory effect of the same drugs on . Therefore, the evaluation of such drugs against may explore the possibility to use to generate species-specific pharmacophore for development of new drugs against .

PubMed: 29324718
DOI: 10.3390/antibiotics7010005

Experimental method

X-RAY DIFFRACTION (2.3 Å)