Enzyme-catalyzed condensation reaction in a mammalian alpha-amylase. High-resolution structural analysis of an enzyme-inhibitor complex

Biochemistry. 2001 Jun 26;40(25):7700-9. doi: 10.1021/bi0102050.

Abstract

Mammalian alpha-amylases catalyze the hydrolysis of alpha-linked glucose polymers according to a complex processive mechanism. We have determined the X-ray structures of porcine pancreatic alpha-amylase complexes with the smallest molecule of the trestatin family (acarviosine-glucose) which inhibits porcine pancreatic alpha-amylase and yet is not hydrolyzed by the enzyme. A structure analysis at 1.38 A resolution of this complex allowed for a clear identification of a genuine single hexasaccharide species composed of two alpha-1,4-linked original molecules bound to the active site of the enzyme. The structural results supported by mass spectrometry experiments provide evidence for an enzymatically catalyzed condensation reaction in the crystal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acarbose / metabolism
  • Amino Sugars / chemistry*
  • Amino Sugars / metabolism*
  • Animals
  • Anions
  • Binding Sites
  • Catalysis
  • Chlorides / metabolism
  • Cold Temperature
  • Computer Simulation
  • Disulfides / chemistry
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism*
  • Humans
  • Hydrolysis
  • Ligands
  • Models, Molecular
  • Pancreas / enzymology
  • Protein Conformation
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Swine
  • alpha-Amylases / antagonists & inhibitors*
  • alpha-Amylases / chemistry*
  • alpha-Amylases / metabolism

Substances

  • Amino Sugars
  • Anions
  • Chlorides
  • Disulfides
  • Enzyme Inhibitors
  • Ligands
  • acarviosine
  • alpha-Amylases
  • Acarbose