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. 2000 Feb 15;346(Pt 1):201–208.

Crystal structures of human pancreatic alpha-amylase in complex with carbohydrate and proteinaceous inhibitors.

V Nahoum 1, G Roux 1, V Anton 1, P Rougé 1, A Puigserver 1, H Bischoff 1, B Henrissat 1, F Payan 1
PMCID: PMC1220841  PMID: 10657258

Abstract

Crystal structures of human pancreatic alpha-amylase (HPA) in complex with naturally occurring inhibitors have been solved. The tetrasaccharide acarbose and a pseudo-pentasaccharide of the trestatin family produced identical continuous electron densities corresponding to a pentasaccharide species, spanning the -3 to +2 subsites of the enzyme, presumably resulting from transglycosylation. Binding of the acarviosine core linked to a glucose residue at subsites -1 to +2 appears to be a critical part of the interaction process between alpha-amylases and trestatin-derived inhibitors. Two crystal forms, obtained at different values of pH, for the complex of HPA with the protein inhibitor from Phaseolus vulgaris (alpha-amylase inhibitor) have been solved. The flexible loop typical of the mammalian alpha-amylases was shown to exist in two different conformations, suggesting that loop closure is pH-sensitive. Structural information is provided for the important inhibitor residue, Arg-74, which has not been observed previously in structural analyses.

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Selected References

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