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Magnesium induced structural reorganization in the active site of adenylate kinase.

Kwangho NamAbdul Raafik Arattu ThodikaSonja TischlikChanrith PhoeurkTamás Milán NagyLéon SchierholzJörgen ÅdénPer RogneMalte DrescherA Elisabeth Sauer-ErikssonMagnus Wolf-Watz
Published in: Science advances (2024)
Phosphoryl transfer is a fundamental reaction in cellular signaling and metabolism that requires Mg 2+ as an essential cofactor. While the primary function of Mg 2+ is electrostatic activation of substrates, such as ATP, the full spectrum of catalytic mechanisms exerted by Mg 2+ is not known. In this study, we integrate structural biology methods, molecular dynamic (MD) simulations, phylogeny, and enzymology assays to provide molecular insights into Mg 2+ -dependent structural reorganization in the active site of the metabolic enzyme adenylate kinase. Our results demonstrate that Mg 2+ induces a conformational rearrangement of the substrates (ATP and ADP), resulting in a 30° adjustment of the angle essential for reversible phosphoryl transfer, thereby optimizing it for catalysis. MD simulations revealed transitions between conformational substates that link the fluctuation of the angle to large-scale enzyme dynamics. The findings contribute detailed insight into Mg 2+ activation of enzymes and may be relevant for reversible and irreversible phosphoryl transfer reactions.
Keyphrases
  • molecular dynamics
  • single molecule
  • molecular dynamics simulations
  • high resolution
  • high throughput
  • high glucose
  • drug induced