Illuminating the structure-function landscape of an evolutionary nonconserved motif in the arginases of Helicobacter gastric pathogens.

The bimetallic enzyme arginase catalyses the conversion of L-arginine to L-ornithine and urea. In Helicobacter pylori (a known human gastric pathogen), this enzyme is an important virulence factor. In spite of the conservation of the catalytic and the metal-binding residues, the H. pylori homolog possesses a 13-residue motif (- ESEEKAWQKLCSL -) present in the middle of the protein sequence, whose role was recently elucidated. Despite several reviews available on arginases, no report has thoroughly illustrated the underlying basis for the importance of the above motif of the H. pylori enzyme in structure and function. In this review, we systematically describe a mechanistic basis for its importance in structure and function based on the known data. This motif of the H. pylori enzyme is present exclusively in the arginases of other Helicobacter gastric pathogens, where the critical residues are conserved, implying that the nonconserved stretch has been selected during the evolution of the enzyme in these gastric pathogens in a specific manner to perform its role in the structure and function. The combined information can be useful for understanding the function of arginases in other Helicobacter gastric pathogens. Additionally, this knowledge can be utilised to screen and design new small molecule inhibitors, specific to the arginases of these pathogens.

© 2023 International Union of Biochemistry and Molecular Biology.