Identification and Preliminary Characterization of a New Chemical Affecting Glucosyltransferase Activities Involved in Plant Cell Wall Biosynthesis

Olga Zabotina, Erik Malm, Georgia Drakakaki, Vincent Bulone, Natasha Raikhel

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Chemical genetics as a part of chemical genomics is a powerful and fast developing approach to dissect biological processes that may be difficult to characterize using conventional genetics because of gene redundancy or lethality and, in the case of polysaccharide biosynthesis, plant flexibility. Polysaccharide synthetic enzymes are located in two main compartments - the Golgi apparatus and plasma membrane - and can be studied in vitro using membrane fractions. Here, we first developed a high-throughput assay that allowed the screening of a library of chemicals with a potential effect on glycosyltransferase activities. Out of the 4800 chemicals screened for their effect on Golgi glucosyltransferases, 66 compounds from the primary screen had an effect on carbohydrate biosynthesis. Ten of these compounds were confirmed to inhibit glucose incorporation after a second screen. One compound exhibiting a strong inhibition effect (ID 6240780 named chemical A) was selected and further studied. It reversibly inhibits the transfer of glucose from UDP-glucose by Golgi membranes, but activates the plasma membrane-bound callose synthase. The inhibition effect is dependent on the chemical structure of the compound, which does not affect endomembrane morphology of the plant cells, but causes changes in cell wall composition. Chemical A represents a novel drug with a great potential for the study of the mechanisms of Golgi and plasma membrane-bound glucosyltransferases.

Original languageEnglish
Pages (from-to)977-989
Number of pages13
JournalMolecular Plant
Volume1
Issue number6
DOIs
Publication statusPublished - Nov 2008
Externally publishedYes

Keywords

  • Callose synthase
  • Cell walls
  • Chemical screening and identification
  • Glycosyltransferase
  • Golgi
  • Plasma membrane

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