title: Structural insight into β-Clamp and its interaction with DNA Ligase in Helicobacter pylori.
abstract: 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.
authors: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.|Department of Bioscience and Biotechnology, Banasthali University, Rajasthan, India.
authors: Preeti
authors: P
authors: Pandey
authors: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors: Khaja Faisal
authors: KF
authors: Tarique
authors: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors: Mohit
authors: M
authors: Mazumder
authors: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors: Syed Arif Abdul
authors: SA
authors: Rehman
authors: Department of Bioscience and Biotechnology, Banasthali University, Rajasthan, India.
authors: Nilima
authors: N
authors: Kumari
authors: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors: Samudrala
authors: S
authors: Gourinath
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D011088:DNA Ligases / Q000737:chemistry*; D016480:Helicobacter pylori / Q000201:enzymology*; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D011088:DNA Ligases