Leishmania donovani adenylosuccinate synthetase requires IMP for dimerization and organization of the active site.

Autor: Mochi JA; School of Life Sciences, Central University of Gujarat, Gandhinagar, India., Jani J; School of Life Sciences, Central University of Gujarat, Gandhinagar, India., Shah S; School of Life Sciences, Central University of Gujarat, Gandhinagar, India., Pappachan A; School of Life Sciences, Central University of Gujarat, Gandhinagar, India.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2024 Oct 27. Date of Electronic Publication: 2024 Oct 27.
DOI: 10.1002/1873-3468.15040
Abstrakt: 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.
(© 2024 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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