3E3L

The R-state Glycogen Phosphorylase

Summary for 3E3L

• Entry DOI: 10.2210/pdb3e3l/pdb
• Related: 3E3N 3E3O 9gpb
• Descriptor: Glycogen phosphorylase, muscle form, SULFATE ION (3 entities in total)
• Functional Keywords: glycogenolysis, inhibition, type 2 diabetes, allosteric enzyme, carbohydrate metabolism, glycogen metabolism, glycosyltransferase, nucleotide-binding, phosphoprotein, pyridoxal phosphate, transferase
• Biological source: Oryctolagus cuniculus (European rabbit,Japanese white rabbit,domestic rabbit,rabbits)
• Total number of polymer chains: 4
• Total formula weight: 391230.04

Authors

Leonidas, D.D.,Zographos, S.E.,Oikonomakos, N.G. (deposition date: 2008-08-07, release date: 2009-02-10, Last modification date: 2023-11-15)

Primary citation

Leonidas, D.D.,Zographos, S.E.,Tsitsanou, K.E.,Skamnaki, V.T.,Stravodimos, G.,Kyriakis, E.
Glycogen phosphorylase revisited: extending the resolution of the R- and T-state structures of the free enzyme and in complex with allosteric activators.
Acta Crystallogr.,Sect.F, 77:303-311, 2021

PubMed Abstract: The crystal structures of free T-state and R-state glycogen phosphorylase (GP) and of R-state GP in complex with the allosteric activators IMP and AMP are reported at improved resolution. GP is a validated pharmaceutical target for the development of antihyperglycaemic agents, and the reported structures may have a significant impact on structure-based drug-design efforts. Comparisons with previously reported structures at lower resolution reveal the detailed conformation of important structural features in the allosteric transition of GP from the T-state to the R-state. The conformation of the N-terminal segment (residues 7-17), the position of which was not located in previous T-state structures, was revealed to form an α-helix (now termed α0). The conformation of this segment (which contains Ser14, phosphorylation of which leads to the activation of GP) is significantly different between the T-state and the R-state, pointing in opposite directions. In the T-state it is packed between helices α4 and α16 (residues 104-115 and 497-508, respectively), while in the R-state it is packed against helix α1 (residues 22'-38') and towards the loop connecting helices α4' and α5' of the neighbouring subunit. The allosteric binding site where AMP and IMP bind is formed by the ordering of a loop (residues 313-326) which is disordered in the free structure, and adopts a conformation dictated mainly by the type of nucleotide that binds at this site.

PubMed: 34473107
DOI: 10.1107/S2053230X21008542

Experimental method

X-RAY DIFFRACTION (2.59 Å)