Structural highlights
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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
A series of substituted 3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors, which have potential as antidiabetic agents, is described. Initial members of the series showed good enzyme inhibitory potency but poor physical properties. Optimisation of the 1-substituent led to 2,3-dihydroxypropyl compounds which showed good in vitro potency and improved physical properties, together with good DMPK profiles and acute in vivo efficacy in a rat model. X-ray crystallographic data are presented, showing an unexpected variety of binding orientations at the dimer interface site.
Development of potent, orally active 1-substituted-3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors.,Birch AM, Kenny PW, Oikonomakos NG, Otterbein L, Schofield P, Whittamore PR, Whalley DP Bioorg Med Chem Lett. 2007 Jan 15;17(2):394-9. Epub 2006 Oct 19. PMID:17095214[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Birch AM, Kenny PW, Oikonomakos NG, Otterbein L, Schofield P, Whittamore PR, Whalley DP. Development of potent, orally active 1-substituted-3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors. Bioorg Med Chem Lett. 2007 Jan 15;17(2):394-9. Epub 2006 Oct 19. PMID:17095214 doi:10.1016/j.bmcl.2006.10.037
