5LRE

Crystal structure of Glycogen Phosphorylase b in complex with KS382

Summary for 5LRE

• Entry DOI: 10.2210/pdb5lre/pdb
• Related: 5LRD
• Descriptor: Glycogen phosphorylase, muscle form, (2~{R},3~{S},4~{R},5~{R},6~{S})-2-(hydroxymethyl)-6-(3-naphthalen-2-yl-1~{H}-1,2,4-triazol-5-yl)oxane-3,4,5-triol, PYRIDOXAL-5'-PHOSPHATE, ... (5 entities in total)
• Functional Keywords: transferase, alpha and beta protein
• Biological source: Oryctolagus cuniculus (Rabbit)
• Total number of polymer chains: 1
• Total formula weight: 98409.33

Authors

Kantsadi, A.L.,Stravodimos, G.A.,Kyriakis, E.,Chatzileontiadou, D.S.M.,Leonidas, D.D. (deposition date: 2016-08-18, release date: 2017-05-31, Last modification date: 2018-01-17)

Primary citation

Kantsadi, A.L.,Bokor, E.,Kun, S.,Stravodimos, G.A.,Chatzileontiadou, D.S.,Leonidas, D.D.,Juhasz-Toth, E.,Szakacs, A.,Batta, G.,Docsa, T.,Gergely, P.,Somsak, L.
Synthetic, enzyme kinetic, and protein crystallographic studies of C-beta-d-glucopyranosyl pyrroles and imidazoles reveal and explain low nanomolar inhibition of human liver glycogen phosphorylase.
Eur J Med Chem, 123:737-745, 2016

PubMed Abstract: C-β-d-Glucopyranosyl pyrrole derivatives were prepared in the reactions of pyrrole, 2-, and 3-aryl-pyrroles with O-peracetylated β-d-glucopyranosyl trichloroacetimidate, while 2-(β-d-glucopyranosyl) indole was obtained by a cross coupling of O-perbenzylated β-d-glucopyranosyl acetylene with N-tosyl-2-iodoaniline followed by spontaneous ring closure. An improved synthesis of O-perbenzoylated 2-(β-d-glucopyranosyl) imidazoles was achieved by reacting C-glucopyranosyl formimidates with α-aminoketones. The deprotected compounds were assayed with isoforms of glycogen phosphorylase (GP) to show no activity of the pyrroles against rabbit muscle GPb. The imidazoles proved to be the best known glucose derived inhibitors of not only the muscle enzymes (both a and b) but also of the pharmacologically relevant human liver GPa (Ki = 156 and 26 nM for the 4(5)-phenyl and -(2-naphthyl) derivatives, respectively). An X-ray crystallographic study of the rmGPb-imidazole complexes revealed structural features of the strong binding, and also allowed to explain the absence of inhibition for the pyrrole derivatives.

PubMed: 27522507
DOI: 10.1016/j.ejmech.2016.06.049

Experimental method

X-RAY DIFFRACTION (1.8 Å)