6qa6

Glycogen Phosphorylase b in complex with 30

spinqualitylabelsall models 6qa6, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6qa6 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 2.4Å Ligands: DMS, HT8, PLP 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 Epimeric series of aryl-substituted glucopyranosylidene-spiro-imidazolinones, an unprecedented new ring system, were synthesized from the corresponding Schiff bases of O-perbenzoylated (gluculopyranosylamine)onamides by intramolecular ring closure of the aldimine moieties with the carboxamide group elicited by N-bromosuccinimide in pyridine. Test compounds were obtained by Zemplen O-debenzoylation. Stereochemistry and ring tautomers of the new compounds were investigated by NMR, time-dependent density functional theory (TDDFT)-electronic circular dichroism, and DFT-NMR methods. Kinetic studies with rabbit muscle and human liver glycogen phosphorylases showed that the ( R)-imidazolinones were 14-216 times more potent than the ( S) epimers. The 2-naphthyl-substituted ( R)-imidazolinone was the best inhibitor of the human enzyme ( Ki 1.7 muM) and also acted on HepG2 cells (IC50 177 muM). X-ray crystallography revealed that only the ( R) epimers bound in the crystal. Their inhibitory efficacy is based on the hydrogen-bonding interactions of the carbonyl oxygen and the NH of the imidazolinone ring. Glucopyranosylidene-spiro-imidazolinones, a New Ring System: Synthesis and Evaluation as Glycogen Phosphorylase Inhibitors by Enzyme Kinetics and X-ray Crystallography.,Szabo KE, Kyriakis E, Psarra AG, Karra AG, Sipos A, Docsa T, Stravodimos GA, Katsidou E, Skamnaki VT, Liggri PGV, Zographos SE, Mandi A, Kiraly SB, Kurtan T, Leonidas DD, Somsak L J Med Chem. 2019 Jun 28. doi: 10.1021/acs.jmedchem.9b00356. PMID:31251604 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glycogen phosphorylase 3D structures

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