Structural insight into β-Clamp and its interaction with DNA Ligase in Helicobacter pylori

• Published in: Scientific reports 2016-08, Vol.6 (1), p.31181-31181, Article 31181
• Main Authors: Pandey, Preeti, Tarique, Khaja Faisal, Mazumder, Mohit, Rehman, Syed Arif Abdul, kumari, Nilima, Gourinath, Samudrala
• Format: Article
• Language: English
• Subjects: 631/45/612/1229; 631/535/1266; 82; 82/103; 82/80; 82/83; Humanities and Social Sciences; multidisciplinary; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep31181

Helicobacter pylori, a gram-negative and microaerophilic bacterium, is the major cause of chronic gastritis, gastric ulcers and gastric cancer. Owing to its central role, DNA replication machinery has emerged as a prime target for the development of antimicrobial drugs. Here, we report 2Å structure of β-clamp from H. pylori (Hpβ-clamp), which is one of the critical components of DNA polymerase III. Despite of similarity in the overall fold of eubacterial β-clamp structures, some distinct features in DNA interacting loops exists that have not been reported previously. The in silico prediction identified the potential binders of β-clamp such as alpha subunit of DNA pol III and DNA ligase with identification of β-clamp binding regions in them and validated by SPR studies. Hpβ-clamp interacts with DNA ligase in micromolar binding affinity. Moreover, we have successfully determined the co-crystal structure of β-clamp with peptide from DNA ligase (not reported earlier in prokaryotes) revealing the region from ligase that interacts with β-clamp.