Structural highlights
5kez is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| NonStd Res: | , , , |
| Related: | 4x9y, 4w93, 1cpu |
| Activity: | Alpha-amylase, with EC number 3.2.1.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
Human pancreatic alpha-amylase (HPA) is responsible for degrading starch to malto-oligosaccharides, thence to glucose, and is therefore an attractive therapeutic target for the treatment of diabetes and obesity. Here we report the discovery of a unique lariat nonapeptide, by means of the RaPID (Random non-standard Peptides Integrated Discovery) system, composed of five amino acids in a head-to-side-chain thioether macrocycle and a further four amino acids in a 310 helical C terminus. This is a potent inhibitor of HPA (Ki = 7 nM) yet exhibits selectivity for the target over other glycosidases tested. Structural studies show that this nonapeptide forms a compact tertiary structure, and illustrate that a general inhibitory motif involving two phenolic groups is often accessed for tight binding of inhibitors to HPA. Furthermore, the work reported here demonstrates the potential of this methodology for the discovery of de novo peptide inhibitors against other glycosidases.
Rapid Discovery of Potent and Selective Glycosidase-Inhibiting De Novo Peptides.,Jongkees SA, Caner S, Tysoe C, Brayer GD, Withers SG, Suga H Cell Chem Biol. 2017 Mar 16;24(3):381-390. doi: 10.1016/j.chembiol.2017.02.001., Epub 2017 Mar 2. PMID:28262556[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jongkees SA, Caner S, Tysoe C, Brayer GD, Withers SG, Suga H. Rapid Discovery of Potent and Selective Glycosidase-Inhibiting De Novo Peptides. Cell Chem Biol. 2017 Mar 16;24(3):381-390. doi: 10.1016/j.chembiol.2017.02.001., Epub 2017 Mar 2. PMID:28262556 doi:http://dx.doi.org/10.1016/j.chembiol.2017.02.001
