Use of biomolecular interaction analysis to elucidate the regulatory mechanism of the cysteine synthase complex from Arabidopsis thaliana

J Biol Chem. 2002 Aug 23;277(34):30629-34. doi: 10.1074/jbc.M111632200. Epub 2002 Jun 12.

Abstract

Real time biomolecular interaction analysis based on surface plasmon resonance has been proven useful for studying protein-protein interaction but has not been extended so far to investigate enzyme-enzyme interactions, especially as pertaining to regulation of metabolic activity. We have applied BIAcore technology to study the regulation of enzyme-enzyme interaction during mitochondrial cysteine biosynthesis in Arabidopsis thaliana. The association of the two enzyme subunits in the hetero-oligomeric cysteine synthase complex was investigated with respect to the reaction intermediate and putative effector O-acetylserine. We have determined an equilibrium dissociation constant of the cysteine synthase complex (K(D) = 25 +/- 4 x 10(-9) m), based on a reliable A + B <--> AB model of interaction. Analysis of dissociation kinetics in the presence of O-acetylserine revealed a half-maximal dissociation rate at 77 +/- 4 microm O-acetylserine and strong positive cooperativity for complex dissociation. The equilibrium of interaction was determined using an enzyme activity-based approach and yielded a K(m) value of 58 +/- 7 microm O-acetylserine. Both effector concentrations are in the range of intracellular O-acetylserine fluctuations and support a functional model that integrates effector-driven cysteine synthase complex dissociation as a regulatory switch for the biosynthetic pathway. The results show that BIAcore technology can be applied to obtain quantitative kinetic data of a hetero-oligomeric protein complex with enzymatic and regulatory function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / metabolism
  • Arabidopsis / enzymology*
  • Arabidopsis Proteins / chemistry*
  • Cysteine Synthase / chemistry*
  • Cysteine Synthase / physiology
  • Kinetics
  • Serine / analogs & derivatives*
  • Serine / metabolism
  • Serine O-Acetyltransferase

Substances

  • Arabidopsis Proteins
  • Serine
  • Acetyltransferases
  • Serine O-Acetyltransferase
  • Cysteine Synthase
  • O-acetylserine