Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Glycogen phosphorylase revisited: Extending the resolution of the R- and T-state structures of the free enzyme and in complex with allosteric activators
Δημιουργός/Συγγραφέας:	Leonidas, Demetres D [EL] Ζωγράφος, Σπύρος Ε.[EN] Zographos, Spyros E. Tsitsanou, Katerina E Skamnaki, Vassiliki T Stravodimos, George Kyriakis, Efthimios
Εκδότης:	International Union of Crystallography
Ημερομηνία:	2021-09-01
Γλώσσα:	Αγγλικά
ISSN:	2053-230X
DOI:	10.1107/S2053230X21008542
Άλλο:	34473107
Περίληψη:	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.
Τίτλος πηγής δημοσίευσης:	Acta crystallographica. Section F, Structural biology communications
Τόμος/Κεφάλαιο:	77
Τεύχος:	Pt 9
Σελίδες:	303-311
Θεματική Κατηγορία:	[EL] Κρυσταλλογραφία[EN] Crystallography [EL] Δομική Βιολογία[EN] Structural Biology [EL] Χημική Βιολογία[EN] Chemical Biology [EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	Allosteric transitions Glycogen metabolism Glycogen phosphorylase Animals Rabbits Allosteric Regulation Crystallography, X-Ray Models, Molecular Muscle Proteins Protein Conformation Substrate Specificity Adenosine Monophosphate Glycogen Phosphorylase Muscles
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2021 by the Authors
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://scripts.iucr.org/cgi-bin/paper?S2053230X21008542
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://journals.iucr.org/f/
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο