2QN1

Glycogen Phosphorylase b in complex with asiatic acid

Summary for 2QN1

• Entry DOI: 10.2210/pdb2qn1/pdb
• Related: 2QN2
• Descriptor: Glycogen phosphorylase, muscle form, asiatic acid (3 entities in total)
• Functional Keywords: glycogenolysis, type 2 diabetes, transferase, apoptosis
• Biological source: Oryctolagus cuniculus (rabbit)
• Total number of polymer chains: 1
• Total formula weight: 98008.02

Authors

Zographos, S.E.,Leonidas, D.D.,Alexacou, K.-M.,Hayes, J.,Oikonomakos, N.G. (deposition date: 2007-07-17, release date: 2008-06-03, Last modification date: 2023-11-15)

Primary citation

Wen, X.,Sun, H.,Liu, J.,Cheng, K.,Zhang, P.,Zhang, L.,Hao, J.,Zhang, L.,Ni, P.,Zographos, S.E.,Leonidas, D.D.,Alexacou, K.-M.,Gimisis, T.,Hayes, J.M.,Oikonomakos, N.G.
Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: synthesis, structure-activity relationships, and X-ray crystallographic studies
J.Med.Chem., 51:3540-3554, 2008

PubMed Abstract: Twenty-five naturally occurring pentacyclic triterpenes, 15 of which were synthesized in this study, were biologically evaluated as inhibitors of rabbit muscle glycogen phosphorylase a (GPa). From SAR studies, the presence of a sugar moiety in triterpene saponins resulted in a markedly decreased activity ( 7, 18- 20) or no activity ( 21, 22). These saponins, however, might find their value as potential natural prodrugs which are much more water-soluble than their corresponding aglycones. To elucidate the mechanism of GP inhibition, we have determined the crystal structures of the GPb-asiatic acid and GPb-maslinic acid complexes. The X-ray analysis indicates that the inhibitors bind at the allosteric activator site, where the physiological activator AMP binds. Pentacyclic triterpenes represent a promising class of multiple-target antidiabetic agents that exert hypoglycemic effects, at least in part, through GP inhibition.

PubMed: 18517260
DOI: 10.1021/jm8000949

Experimental method

X-RAY DIFFRACTION (2.401 Å)