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Activation of human liver glycogen phosphorylase by alteration of the secondary structure and packing of the catalytic core.

Rath VL, Ammirati M, LeMotte PK, Fennell KF, Mansour MN, Danley DE, Hynes TR, Schulte GK, Wasilko DJ, Pandit J
Mol Cell 6 139-48 (2000)
Cited: 65 times
EuropePMC logo PMID: 10949035

Abstract

Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1-phosphate, which enters glycolysis to fulfill the energetic requirements of the organism. Maintaining control of blood glucose levels is critical in minimizing the debilitating effects of diabetes, making liver glycogen phosphorylase a potential therapeutic target. To support inhibitor design, we determined the crystal structures of the active and inactive forms of human liver glycogen phosphorylase a. During activation, forty residues of the catalytic site undergo order/disorder transitions, changes in secondary structure, or packing to reorganize the catalytic site for substrate binding and catalysis. Knowing the inactive and active conformations of the liver enzyme and how each differs from its counterpart in muscle phosphorylase provides the basis for designing inhibitors that bind preferentially to the inactive conformation of the liver isozyme.

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  1. Structural Basis for Allostery in PLP-dependent Enzymes. Tran JU, Brown BL. Front Mol Biosci 9 884281 (2022)

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Reviews citing this publication (18)

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Articles citing this publication (40)

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  33. Beta-Sitosterol Facilitates GLUT4 Vesicle Fusion on the Plasma Membrane via the Activation of Rab/IRAP/Munc 18 Signaling Pathways in Diabetic Gastrocnemius Muscle of Adult Male Rats. Pei J, Prasad M, Mohamed Helal G, El-Sherbiny M, Abdelmonem Elsherbini DM, Rajagopal P, Palanisamy CP, Veeraraghavan VP, Jayaraman S, Surapaneni KM. Bioinorg Chem Appl 2022 7772305 (2022)
  34. Lysine Decarboxylase with an Enhanced Affinity for Pyridoxal 5-Phosphate by Disulfide Bond-Mediated Spatial Reconstitution. Sagong HY, Kim KJ. PLoS One 12 e0170163 (2017)
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