2ZB2

Human liver glycogen phosphorylase a complexed with glcose and 5-chloro-N-[4-(1,2-dihydroxyethyl)phenyl]-1H-indole-2-carboxamide

Summary for 2ZB2

• Entry DOI: 10.2210/pdb2zb2/pdb
• Descriptor: Glycogen phosphorylase, liver form, alpha-D-glucopyranose, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (7 entities in total)
• Functional Keywords: allosteric site, allosteric binding, allosteric enzyme, carbohydrate metabolism, disease mutation, glycogen metabolism, glycogen storage disease, glycosyltransferase, nucleotide-binding, phosphorylation, pyridoxal phosphate, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 196984.15

Authors

Katayama, N.,Onda, K. (deposition date: 2007-10-15, release date: 2008-09-02, Last modification date: 2023-11-01)

Primary citation

Onda, K.,Suzuki, T.,Shiraki, R.,Yonetoku, Y.,Negoro, K.,Momose, K.,Katayama, N.,Orita, M.,Yamaguchi, T.,Ohta, M.,Tsukamoto, S.
Synthesis of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives as inhibitors of human liver glycogen phosphorylase a.
Bioorg.Med.Chem., 16:5452-5464, 2008

PubMed Abstract: A series of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives were prepared and evaluated as inhibitors of human liver glycogen phosphorylase a (hLGPa). One compound, 5-chloro-N-[4-(1,2-dihydroxyethyl)phenyl]-1H-indole-2-carboxamide (2f), inhibited hLGPa with an IC(50) of 0.90microM. The pyridine analogue of 2f showed inhibitory activity of glucagon-induced glucose output in cultured primary hepatocytes with an IC(50) of 0.62microM and oral hypoglycemic activity in diabetic db/db mice. Crystallographic determination of the complex of 2f with hLGPa showed binding of the inhibitor in a solvent cavity at the dimer interface, with the two hydroxyl groups making favorable electrostatic interactions with hLGPa.

PubMed: 18434170
DOI: 10.1016/j.bmc.2008.04.010

Experimental method

X-RAY DIFFRACTION (2.45 Å)