Dilip, HarithaHarithaDilipPurushothaman, GayathriGayathriPurushothamanSharma, GauravGauravSharmaMenon, AishwaryaAishwaryaMenonThiruvenkatam, VijayVijayThiruvenkatamKirubakaran, SivapriyaSivapriyaKirubakaran2025-08-312025-08-312022-05-0210.1002/asia.2022001252-s2.0-85127293323https://d8.irins.org/handle/IITG2025/2608135293683The emergence of antibiotic-resistant strains of Helicobacter pylori necessitates the development of novel therapeutic strategies to fight against its infection. Recently, the enzyme inosine-5′-monophosphate dehydrogenase (IMPDH) has emerged as a promising target to treat bacterial infections due to its crucial role in the de novo purine biosynthesis pathway. The differences between the prokaryotic and eukaryotic IMPDHs, in the NAD⁺ binding domain and flap region, allow the identification of pathogen-specific inhibitors. In the present study, seven point mutants of wild type Helicobacter pylori IMPDH are constructed by site-directed mutagenesis, and characterized using in silico and kinetic studies. Point mutations in the NAD⁺ binding domain and the flap region are shown to impart significant changes in the enzyme's structure and function. In addition, the product inhibition characteristics of the Arg396-Tyr397 dyad (RY dyad) show that both the residues are important for water activation in the reaction. The results obtained are beneficial for the design and development of small-molecule inhibitors, capable of species-specific inhibition.falseHelicobacter pylori | homology modeling | IMPDH | point mutation | site-directed mutagenesisArticle1861471X2 May 20220e202200125arJournal0WOS:000773996100001