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

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, s...

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Bibliographic Details
Published in:Biochemical journal 2000-02, Vol.346 Pt 1 (1), p.201-208
Main Authors: Nahoum, V, Roux, G, Anton, V, Rougé, P, Puigserver, A, Bischoff, H, Henrissat, B, Payan, F
Format: Article
Language:English
Subjects:
Acarbose - chemistry
Acarbose - metabolism
Acarbose - pharmacology
alpha-Amylases - antagonists & inhibitors
alpha-Amylases - chemistry
alpha-Amylases - metabolism
Amino Sugars - metabolism
Amino Sugars - pharmacology
Arginine - chemistry
Arginine - metabolism
Binding Sites
Biochemistry, Molecular Biology
Crystallography, X-Ray
Electrons
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - metabolism
Enzyme Inhibitors - pharmacology
Glycosylation
Humans
Hydrogen Bonding
Hydrogen-Ion Concentration
Lectins - chemistry
Lectins - metabolism
Lectins - pharmacology
Life Sciences
Models, Molecular
Molecular Sequence Data
Pancreas - enzymology
Plant Lectins
Plant Proteins - chemistry
Plant Proteins - metabolism
Plant Proteins - pharmacology
Polysaccharides - chemistry
Polysaccharides - metabolism
Polysaccharides - pharmacology
Protein Conformation
Structural Biology
Trisaccharides - chemistry
Trisaccharides - metabolism
Trisaccharides - pharmacology
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Summary: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.
ISSN:0264-6021
1470-8728
DOI:10.1042/0264-6021:3460201