6S4H
The crystal structure of glycogen phosphorylase in complex with 8
Summary for 6S4H
| Entry DOI | 10.2210/pdb6s4h/pdb |
| Descriptor | Glycogen phosphorylase, muscle form, (2~{R},3~{S},4~{R},5~{R},6~{S})-2-(hydroxymethyl)-6-(2-phenyl-1~{H}-imidazol-4-yl)oxane-3,4,5-triol, DIMETHYL SULFOXIDE, ... (5 entities in total) |
| Functional Keywords | phosphorylase, inhibitor, c-beta-d-glucopyranosyl imidazole, transferase |
| Biological source | Oryctolagus cuniculus (Rabbit) |
| Total number of polymer chains | 1 |
| Total formula weight | 98053.99 |
| Authors | Kyriakis, E.,Solovou, T.G.A.,Papaioannou, O.S.E.,Skamnaki, V.T.,Leonidas, D.D. (deposition date: 2019-06-28, release date: 2020-02-19) |
| Primary citation | Kyriakis, E.,Karra, A.G.,Papaioannou, O.,Solovou, T.,Skamnaki, V.T.,Liggri, P.G.V.,Zographos, S.E.,Szennyes, E.,Bokor, E.,Kun, S.,Psarra, A.G.,Somsak, L.,Leonidas, D.D. The architecture of hydrogen and sulfur sigma-hole interactions explain differences in the inhibitory potency of C-beta-d-glucopyranosyl thiazoles, imidazoles and an N-beta-d glucopyranosyl tetrazole for human liver glycogen phosphorylase and offer new insights to structure-based design. Bioorg.Med.Chem., 28:115196-115196, 2020 Cited by PubMed Abstract: C-Glucopyranosyl imidazoles, thiazoles, and an N-glucopyranosyl tetrazole were assessed in vitro and ex vivo for their inhibitory efficiency against isoforms of glycogen phosphorylase (GP; a validated pharmacological target for the development of anti-hyperglycaemic agents). Imidazoles proved to be more potent inhibitors than the corresponding thiazoles or the tetrazole. The most potent derivative has a 2-naphthyl substituent, a K value of 3.2 µM for hepatic glycogen phosphorylase, displaying also 60% inhibition of GP activity in HepG2 cells, compared to control vehicle treated cells, at 100 μM. X-Ray crystallography studies of the protein - inhibitor complexes revealed the importance of the architecture of inhibitor associated hydrogen bonds or sulfur σ-hole bond interactions to Asn284 OD1, offering new insights to structure-based design efforts. Moreover, while the 2-glucopyranosyl-tetrazole seems to bind differently from the corresponding 1,2,3-triazole compound, the two inhibitors are equipotent. PubMed: 31767404DOI: 10.1016/j.bmc.2019.115196 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.45 Å) |
Structure validation
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