5FXT
Crystal Structure of Helicobacter pylori beta clamp in complex with Carprofen
Summary for 5FXT
| Entry DOI | 10.2210/pdb5fxt/pdb |
| Descriptor | DNA POLYMERASE III SUBUNIT BETA, (2S)-2-(6-chloro-9H-carbazol-2-yl)propanoic acid (3 entities in total) |
| Functional Keywords | transferase, dna clamp, sliding clamp |
| Biological source | HELICOBACTER PYLORI (CAMPYLOBACTER PYLORI) |
| Total number of polymer chains | 1 |
| Total formula weight | 42512.15 |
| Authors | Pandey, P.,Gourinath, S. (deposition date: 2016-03-02, release date: 2017-08-16, 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 Cited by 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: 29324718DOI: 10.3390/antibiotics7010005 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.97 Å) |
Structure validation
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