Allosterically gated enzyme dynamics in the cysteine synthase complex regulate cysteine biosynthesis in Arabidopsis thaliana

Structure. 2012 Feb 8;20(2):292-302. doi: 10.1016/j.str.2011.11.019.


Plants and bacteria assimilate sulfur into cysteine. Cysteine biosynthesis involves a bienzyme complex, the cysteine synthase complex (CSC), which consists of serine-acetyl-transferase (SAT) and O-acetyl-serine-(thiol)-lyase (OAS-TL) enzymes. The activity of OAS-TL is reduced by formation of the CSC. Although this reduction is an inherent part of the self-regulation cycle of cysteine biosynthesis, there has until now been no explanation as to how OAS-TL loses activity in plants. Complexation of SAT and OAS-TL involves binding of the C-terminal tail of SAT in one of the active sites of the homodimeric OAS-TL. We here explore the flexibility of the unoccupied active site in Arabidopsis thaliana cytosolic and mitochondrial OAS-TLs. Our results reveal two gates in the OAS-TL active site that define its accessibility. The observed dynamics of the gates show allosteric closure of the unoccupied active site of OAS-TL in the CSC, which can hinder substrate binding, abolishing its turnover to cysteine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Amino Acid Motifs
  • Arabidopsis / enzymology*
  • Arabidopsis Proteins / chemistry*
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cysteine / biosynthesis*
  • Cysteine Synthase / chemistry*
  • Mitochondria / enzymology*
  • Molecular Dynamics Simulation
  • Peptide Fragments / chemistry
  • Protein Binding
  • Protein Structure, Quaternary
  • Serine O-Acetyltransferase / chemistry


  • Arabidopsis Proteins
  • Peptide Fragments
  • Serine O-Acetyltransferase
  • Cysteine Synthase
  • Cysteine

Associated data

  • PDB/4AEC