PDBsum entry 1u33

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Hydrolase PDB id
Protein chain
496 a.a. *
Waters ×268
* Residue conservation analysis

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Key reference
Title In situ extension as an approach for identifying novel alpha-Amylase inhibitors.
Authors S.Numao, I.Damager, C.Li, T.M.Wrodnigg, A.Begum, C.M.Overall, G.D.Brayer, S.G.Withers.
Ref. J Biol Chem, 2004, 279, 48282-48291. [DOI no: 10.1074/jbc.M406804200]
PubMed id 15304511
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.
Figure 8.
FIG. 8. Stereo drawings illustrating the bound conformations of the inhibitors GHIL (a), GHIL/G3F product (b), and acarbose (c) in the active site of HPA. Only selected active site residues are shown for clarity.
Figure 9.
FIG. 9. Schematic diagrams illustrating the hydrogen bonding interactions ( 3.5 Å) formed in the active site of HPA by GHIL (a), G2-GHIL formed on incubation with GHIL and G3F (b), and acarbose (c). The subsites of HPA occupied by each bound moiety are indicated, and interacting amino acids are designated with their one-letter codes.
The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 48282-48291) copyright 2004.
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