dc.creator | Leonidas D.D., Zographos S.E., Tsitsanou K.E., Skamnaki V.T., Stravodimos G., Kyriakis E. | en |
dc.date.accessioned | 2023-01-31T08:49:43Z | |
dc.date.available | 2023-01-31T08:49:43Z | |
dc.date.issued | 2021 | |
dc.identifier | 10.1107/S2053230X21008542 | |
dc.identifier.issn | 2053230X | |
dc.identifier.uri | http://hdl.handle.net/11615/75765 | |
dc.description.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. © 2021. | en |
dc.language.iso | en | en |
dc.source | Acta Crystallographica Section F: Structural Biology Communications | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85114323374&doi=10.1107%2fS2053230X21008542&partnerID=40&md5=ec37b56d8c186b0ac5b06fa57e15e60a | |
dc.subject | adenosine phosphate | en |
dc.subject | glycogen phosphorylase | en |
dc.subject | inosine phosphate | en |
dc.subject | muscle protein | en |
dc.subject | allosterism | en |
dc.subject | animal | en |
dc.subject | chemistry | en |
dc.subject | enzyme specificity | en |
dc.subject | enzymology | en |
dc.subject | Leporidae | en |
dc.subject | metabolism | en |
dc.subject | molecular model | en |
dc.subject | muscle | en |
dc.subject | protein conformation | en |
dc.subject | X ray crystallography | en |
dc.subject | Adenosine Monophosphate | en |
dc.subject | Allosteric Regulation | en |
dc.subject | Animals | en |
dc.subject | Crystallography, X-Ray | en |
dc.subject | Glycogen Phosphorylase | en |
dc.subject | Inosine Monophosphate | en |
dc.subject | Models, Molecular | en |
dc.subject | Muscle Proteins | en |
dc.subject | Muscles | en |
dc.subject | Protein Conformation | en |
dc.subject | Rabbits | en |
dc.subject | Substrate Specificity | en |
dc.subject | International Union of Crystallography | en |
dc.title | Glycogen phosphorylase revisited: Extending the resolution of the R- And T-state structures of the free enzyme and in complex with allosteric activators | en |
dc.type | journalArticle | en |