Structural highlights
Function
[PYGM_RABIT] Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.
Publication Abstract from PubMed
Aryl substituted 1-(beta-D-glucosaminyl)-1,2,3-triazoles as well as C-beta-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-beta-D-glucosaminyl 1,2,3-triazoles showed weak or no inhibition, the C-beta-D-glucosaminyl derivatives had potent activity and the best inhibitor was the 2-(beta-D-glucosaminyl)-4(5)-(2-naphthyl)-imidazole with a Ki 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.
Nanomolar inhibitors of glycogen phosphorylase based on beta-D-glucosaminyl heterocycles: a combined synthetic, enzyme kinetic and protein crystallography study.,Bokor E, Kyriakis E, Solovou TG, Koppany C, Kantsadi AL, Szabo KE, Szakacs A, Stravodimos GA, Docsa T, Skamnaki VT, Zographos SE, Gergely P, Leonidas DD, Somsak L J Med Chem. 2017 Sep 19. doi: 10.1021/acs.jmedchem.7b01056. PMID:28925695[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bokor E, Kyriakis E, Solovou TG, Koppany C, Kantsadi AL, Szabo KE, Szakacs A, Stravodimos GA, Docsa T, Skamnaki VT, Zographos SE, Gergely P, Leonidas DD, 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. 2017 Sep 19. doi: 10.1021/acs.jmedchem.7b01056. PMID:28925695 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b01056
