6EQL

Crystal Structure of Human Glycogenin-1 (GYG1) Tyr195pIPhe mutant complexed with manganese and UDP

6EQL の概要

• エントリーDOI: 10.2210/pdb6eql/pdb
• 分子名称: Glycogenin-1, URIDINE-5'-DIPHOSPHATE, MANGANESE (II) ION, ... (6 entities in total)
• 機能のキーワード: glycogenin-1, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60837.82

構造登録者

Bailey, H.J.,Kopec, J.,Bilyard, M.K.,Bezerra, G.A.,Seo Lee, S.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Davis, B.G.,Yue, W.W. (登録日: 2017-10-13, 公開日: 2017-12-20, 最終更新日: 2025-04-09)

主引用文献

Bilyard, M.K.,Bailey, H.J.,Raich, L.,Gafitescu, M.A.,Machida, T.,Iglesias-Fernandez, J.,Lee, S.S.,Spicer, C.D.,Rovira, C.,Yue, W.W.,Davis, B.G.
Palladium-mediated enzyme activation suggests multiphase initiation of glycogenesis.
Nature, 563:235-240, 2018

PubMed Abstract: Biosynthesis of glycogen, the essential glucose (and hence energy) storage molecule in humans, animals and fungi, is initiated by the glycosyltransferase enzyme, glycogenin (GYG). Deficiencies in glycogen formation cause neurodegenerative and metabolic disease, and mouse knockout and inherited human mutations of GYG impair glycogen synthesis. GYG acts as a 'seed core' for the formation of the glycogen particle by catalysing its own stepwise autoglucosylation to form a covalently bound gluco-oligosaccharide chain at initiation site Tyr 195. Precise mechanistic studies have so far been prevented by an inability to access homogeneous glycoforms of this protein, which unusually acts as both catalyst and substrate. Here we show that unprecedented direct access to different, homogeneously glucosylated states of GYG can be accomplished through a palladium-mediated enzyme activation 'shunt' process using on-protein C-C bond formation. Careful mimicry of GYG intermediates recapitulates catalytic activity at distinct stages, which in turn allows discovery of triphasic kinetics and substrate plasticity in GYG's use of sugar substrates. This reveals a tolerant but 'proof-read' mechanism that underlies the precision of this metabolic process. The present demonstration of direct, chemically controlled access to intermediate states of active enzymes suggests that such ligation-dependent activation could be a powerful tool in the study of mechanism.

PubMed: 30356213
DOI: 10.1038/s41586-018-0644-7

実験手法

X-RAY DIFFRACTION (2.38 Å)