6eql | pdb_00006eql

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

spinqualitylabelsall models 6eql, resolution 2.38Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6eql is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.38Å Ligands: 2PE, EDO, MN, PHI, UDP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GLYG_HUMAN Glycogen storage disease due to glycogenin deficiency. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function GLYG_HUMAN Self-glucosylates, via an inter-subunit mechanism, to form an oligosaccharide primer that serves as substrate for glycogen synthase. Publication Abstract from PubMed Biosynthesis of glycogen, the essential glucose (and hence energy) storage molecule in humans, animals and fungi(1), is initiated by the glycosyltransferase enzyme, glycogenin (GYG). Deficiencies in glycogen formation cause neurodegenerative and metabolic disease(2-4), and mouse knockout(5) and inherited human mutations(6) 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. Palladium-mediated enzyme activation suggests multiphase initiation of glycogenesis.,Bilyard MK, Bailey HJ, Raich L, Gafitescu MA, Machida T, Iglesias-Fernandez J, Lee SS, Spicer CD, Rovira C, Yue WW, Davis BG Nature. 2018 Oct 24. pii: 10.1038/s41586-018-0644-7. doi:, 10.1038/s41586-018-0644-7. PMID:30356213 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glycogenin

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