5O54

Glycogen Phosphorylase b in complex with 29a

Summary for 5O54

• Entry DOI: 10.2210/pdb5o54/pdb
• Related: 5O50 5O52
• Descriptor: Glycogen phosphorylase, muscle form, PYRIDOXAL-5'-PHOSPHATE, (2~{R},3~{S},4~{R},5~{R},6~{R})-5-azanyl-2-(hydroxymethyl)-6-(5-phenyl-4~{H}-1,2,4-triazol-3-yl)oxane-3,4-diol, ... (5 entities in total)
• Functional Keywords: transferase
• Biological source: Oryctolagus cuniculus (Rabbit)
• Total number of polymer chains: 1
• Total formula weight: 98324.06

Authors

Kyriakis, E.,Solovou, T.G.A.,Stravodimos, G.A.,Kantsadi, A.L.,Chatzileontiadou, D.S.,Skamnaki, V.T.,Leonidas, D.D. (deposition date: 2017-05-31, release date: 2017-09-27, Last modification date: 2017-11-29)

Primary citation

Bokor, E.,Kyriakis, E.,Solovou, T.G.A.,Koppany, C.,Kantsadi, A.L.,Szabo, K.E.,Szakacs, A.,Stravodimos, G.A.,Docsa, T.,Skamnaki, V.T.,Zographos, S.E.,Gergely, P.,Leonidas, D.D.,Somsak, L.
Nanomolar Inhibitors of Glycogen Phosphorylase Based on beta-d-Glucosaminyl Heterocycles: A Combined Synthetic, Enzyme Kinetic, and Protein Crystallography Study.
J. Med. Chem., 60:9251-9262, 2017

PubMed Abstract: Aryl substituted 1-(β-d-glucosaminyl)-1,2,3-triazoles as well as C-β-d-glucosaminyl 1,2,4-triazoles and imidazoles were synthesized and tested as inhibitors against muscle and liver isoforms of glycogen phosphorylase (GP). While the N-β-d-glucosaminyl 1,2,3-triazoles showed weak or no inhibition, the C-β-d-glucosaminyl derivatives had potent activity, and the best inhibitor was the 2-(β-d-glucosaminyl)-4(5)-(2-naphthyl)-imidazole with a K value of 143 nM against human liver GPa. An X-ray crystallography study of the rabbit muscle GPb inhibitor complexes revealed structural features of the strong binding and offered an explanation for the differences in inhibitory potency between glucosyl and glucosaminyl derivatives and also for the differences between imidazole and 1,2,4-triazole analogues.

PubMed: 28925695
DOI: 10.1021/acs.jmedchem.7b01056

Experimental method

X-RAY DIFFRACTION (2.45 Å)