Chemical genetics and cereal starch metabolism: structural basis of the non-covalent and covalent inhibition of barley β-amylase

Mol Biosyst. 2011 Mar;7(3):718-30. doi: 10.1039/c0mb00204f. Epub 2010 Nov 18.


There are major issues regarding the proposed pathway for starch degradation in germinating cereal grain. Given the commercial importance but genetic intractability of the problem, we have embarked on a program of chemical genetics studies to identify and dissect the pathway and regulation of starch degradation in germinating barley grains. As a precursor to in vivo studies, here we report systematic analysis of the reversible and irreversible inhibition of the major β-amylase of the grain endosperm (BMY1). The molecular basis of inhibitor action was defined through high resolution X-ray crystallography studies of unliganded barley β-amylase, as well as its complexes with glycone site binder disaccharide iminosugar G1M, irreversible inhibitors α-epoxypropyl and α-epoxybutyl glucosides, which target the enzyme's catalytic residues, and the aglycone site binders acarbose and α-cyclodextrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Edible Grain / chemistry
  • Edible Grain / genetics
  • Edible Grain / metabolism*
  • Endosperm / chemistry
  • Endosperm / genetics
  • Endosperm / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Conformation
  • Starch / chemistry
  • Starch / metabolism*
  • Starch / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • beta-Amylase / antagonists & inhibitors*


  • Enzyme Inhibitors
  • Starch
  • beta-Amylase