Catalytic mechanism of the metal-dependent fuculose aldolase from Escherichia coli as derived from the structure

J Mol Biol. 1996 Jun 14;259(3):458-66. doi: 10.1006/jmbi.1996.0332.

Abstract

The structure of L-fuculose-1-phosphate aldolase in a cubic crystal form has been determined with and without the inhibitor phosphoglycolohydroxamate at 2.4 and 2.7 angstrom (1 angstrom = 0.1 nm) resolution, respectively. This inhibitor mimics the enediolate transition state of the substrate moiety dihydroxyacetone phosphate. The structures showed that dihydroxyacetone phosphate ligates the zinc ion of this metal-dependent class II aldolase with its hydroxyl and keto oxygen atoms, shifting Glu73 away from the zinc coordination sphere to a non-polar environment. At this position Glu73 accepts a proton in the initial reaction step, producing the enediolate which is then stabilized by the zinc ion. The other substrate moiety L-lactaldehyde was modeled, because no binding structure is yet available.

MeSH terms

  • Aldehyde-Lyases / antagonists & inhibitors
  • Aldehyde-Lyases / chemistry*
  • Aldehyde-Lyases / metabolism*
  • Crystallography, X-Ray / methods
  • Escherichia coli / enzymology*
  • Hydroxamic Acids / metabolism
  • Hydroxamic Acids / pharmacology
  • Models, Biological
  • Models, Molecular
  • Protein Conformation

Substances

  • Hydroxamic Acids
  • phosphoglycolohydroxamate
  • Aldehyde-Lyases
  • L-fuculosephosphate aldolase

Associated data

  • PDB/T8142
  • PDB/T8143
  • PDB/T8144
  • PDB/T8145