5lre

Crystal structure of Glycogen Phosphorylase b in complex with KS382Crystal structure of Glycogen Phosphorylase b in complex with KS382

Structural highlights

5lre is a 1 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

C-beta-d-Glucopyranosyl pyrrole derivatives were prepared in the reactions of pyrrole, 2-, and 3-aryl-pyrroles with O-peracetylated beta-d-glucopyranosyl trichloroacetimidate, while 2-(beta-d-glucopyranosyl) indole was obtained by a cross coupling of O-perbenzylated beta-d-glucopyranosyl acetylene with N-tosyl-2-iodoaniline followed by spontaneous ring closure. An improved synthesis of O-perbenzoylated 2-(beta-d-glucopyranosyl) imidazoles was achieved by reacting C-glucopyranosyl formimidates with alpha-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.

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.,Kantsadi AL, Bokor E, Kun S, Stravodimos GA, Chatzileontiadou DS, Leonidas DD, Juhasz-Toth E, Szakacs A, Batta G, Docsa T, Gergely P, Somsak L Eur J Med Chem. 2016 Jul 12;123:737-745. doi: 10.1016/j.ejmech.2016.06.049. PMID:27522507^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kantsadi AL, Bokor E, Kun S, Stravodimos GA, Chatzileontiadou DS, Leonidas DD, 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. 2016 Jul 12;123:737-745. doi: 10.1016/j.ejmech.2016.06.049. PMID:27522507 doi:http://dx.doi.org/10.1016/j.ejmech.2016.06.049

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OCA

[1] Kantsadi AL, Bokor E, Kun S, Stravodimos GA, Chatzileontiadou DS, Leonidas DD, 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. 2016 Jul 12;123:737-745. doi: 10.1016/j.ejmech.2016.06.049. PMID:27522507 doi:http://dx.doi.org/10.1016/j.ejmech.2016.06.049

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