1u33
From Proteopedia
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In situ extension as an approach for identifying novel alpha-amylase inhibitors
Overview
A new approach for the discovery and subsequent structural elucidation of, oligosaccharide-based inhibitors of alpha-amylases based upon, autoglucosylation of known alpha-glucosidase inhibitors is presented. This, concept, highly analogous to what is hypothesized to occur with acarbose, is demonstrated with the known alpha-glucosidase inhibitor, d-gluconohydroximino-1,5-lactam. This was transformed from an inhibitor of, human pancreatic alpha-amylase with a K(i) value of 18 mm to a, trisaccharide analogue with a K(i) value of 25 mum. The three-dimensional, structure of this complex was determined by x-ray crystallography and, represents the first such structure determined with this class of, inhibitors in any alpha-glycosidase. This approach to the discovery and, structural analysis of amylase inhibitors should be generally applicable, to other endoglucosidases and readily adaptable to a high throughput, format.
About this Structure
1U33 is a Single protein structure of sequence from Homo sapiens with NAG, LM2, CA and CL as ligands. Active as Alpha-amylase, with EC number 3.2.1.1 Full crystallographic information is available from OCA.
Reference
In situ extension as an approach for identifying novel alpha-amylase inhibitors., Numao S, Damager I, Li C, Wrodnigg TM, Begum A, Overall CM, Brayer GD, Withers SG, J Biol Chem. 2004 Nov 12;279(46):48282-91. Epub 2004 Aug 10. PMID:15304511
Page seeded by OCA on Mon Nov 12 19:30:50 2007
Categories: Alpha-amylase | Homo sapiens | Single protein | Begum, A. | Brayer, G.D. | Damager, I. | Li, C. | Numao, S. | Overall, C.M. | Withers, S.G. | Wrodnigg, T.M. | CA | CL | LM2 | NAG | Acarbose | Enzyme mechanism | Glucosidase | Glycosidase | Human pancreatic alpha-amylase | Inhibitor
