ANNOUNCEMENTS
Helicobacter pylori (H. pylori) bacterium is a known causative agent of severe gastric diseases. Within the arginine decarboxylase (ADC) pathway of H. pylori , the enzyme CPA is crucial, catalysing the conversion of NCP into putrescine , a precursor for polyamines which is essential for b acterial growth and development. Notably, CPA is exclusive to bacterial homologs and certain plants, with no human counterpart which certainly mak e s it an attractive target for therapeutic intervention. This study focuses on identifying substrate binding r esidues in the CPA enzyme of H. pylori 26695 . Through molecular docking and molecular dynamic simulation of wild type CPA with NCP , Glu126 was hypothesized as a critical substrate binding residue. An in silico CPA mutant E126A was prepared and its molecular docking and dynamic simulation results indicated a significant alteration in substrate binding. To validate this computational hypothesis, the recombinant E126A mutant was prepared . Subsequent enzymatic activity assays revealed that the mutant pr otein exhibited significantly reduced activity compared to the wild type, confirming the essential role of Glu126 in substrate binding. These findings enhance our understanding of the catalytic mechanism of CPA and highlight its potential as a therapeutic target for combating H. pylori infections.
