Saxagliptin: Difference between revisions

<applet  load="" size="480" color="" frame="true"  spin="on" Scene ="Saxagliptin/Saxaglilptin/1" align="right" caption="Saxagliptin, better known as Onglyza, ([[3bjm]])"/>

Dipeptidyl Peptidase-4 (DPP-4) is a membrane serine exopeptidase that cleaves proline dipeptides form the N-terminal end of protein substrates. DPP-4 plays a major role in [[Carbohydrate Metabolism|glucose metabolism]] as it is responsible for the degradation of incretins, most notably Glucagon-like peptide-1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP). Incretins are a group of gastrointestinal hormones that stimulate insulin biosynthesis and inhibit glucagon secretion after consuming high glucose meals. Since [[Diabetes]] is typically caused by a deficiency in [[insulin]] secretion or by increased hepatic glucose production, preventing incretin degradation is a viable treatment approach for diabetics. Saxagliptin is a <scene name='Saxagliptin/Dpp4/1'>competitive inhibitor of DPP-4</scene>. By inhibiting DPP-4 and subsequently preventing the enzymatic degradation of GLP-1 and GIP, these incretins are able to potentiate the secretion of insulin and suppress the release of glucagon by the pancreas, resulting in controlled blood-glucose levels.<ref>PMID:17073841</ref> Saxagliptin binds to the <scene name='Saxagliptin/Act/1'>active site pocket of DPP-4</scene> within a tunnel capable of binding incretin compounds and situating their N-terminus in the active site. <ref>PMID:15634008</ref> This active site contains several <scene name='Saxagliptin/Act2/2'>crucial residues for binding</scene> including: Glu 206, Glu 205, Asp 663, Tyr 662, Asn 710, Val 711, His 740, Trp 629, Ser 630, Try 631, Tyr 547, Tyr 666, & Phe 357.