Jigneshkumar A Mochi, Jaykumar Jani, Smit Shah, Anju Pappachan
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Leishmania donovani adenylosuccinate synthetase requires IMP for dimerization and organization of the active site.
Adenylosuccinate synthetase (AdSS), which catalyses the GTP-dependent conversion of inosine monophosphate (IMP) and aspartic acid to succinyl-AMP, plays a major role in purine biosynthesis. In some bacterial AdSS, it is implicated that IMP binding is important to organize the active site, but in certain plant AdSS, GTP performs this role. Here, we report that in Leishmania donovani AdSS, IMP binding favoured dimerization, induced greater conformational change and improved the protein stability more than GTP binding. IMP binding, which resulted in a network of hydrogen bonds, stabilized the conformation of active site loops and brought the switch loop to a closed conformation, which then facilitated GTP binding. Our results provide a basis for designing better inhibitors of leishmanial AdSS.
期刊介绍:
FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.