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Palladium-mediated enzyme activation suggests multiphase initiation of glycogenesis

M. K. Bilyard, H. Bailey, L. Raich, M. Gafitescu, T. Machida, J. Iglesias-Fernández, S. S. Lee, C. D. Spicer, C. Rovira, W. W. Yue, B. G. Davis.
Nature, 563 (2018) 235.

Glycogen is the key energy storage molecule in humans, animals and fungi. It’s where the glucose that fuels us is stored and release from. At the heart of the glycogen particle there is a protein that starts the glycogen formation catalysing its own autoglucosylation, that is, decorating itself with glucose molecules. This ‘self-sweetening’ protein – called glycogenin – has been hard to understand since it acts as both catalyst and substrate, so it is changing continuously during the process. In this work, we have been able to recapitulate and understand mechanistic activity at different stages using a combination of palladium-mediated enzyme activation and molecular dynamics simulations. The results obtained reveal a surprisingly tolerant but precise process to glycogen’s creation and growth. The new method used in this work allows to “jump” directly into the intermediate states of glycogening through chemical control and could be a powerful tool in the study of enzymes mechanism.