Dynamic and structural characterization of a bacterial FHA protein reveals a new autoinhibition mechanism

Structure. 2009 Apr 15;17(4):568-78. doi: 10.1016/j.str.2009.02.012.


The OdhI protein is key regulator of the TCA cycle in Corynebacterium glutamicum. This highly conserved protein is found in GC rich Gram-positive bacteria (e.g., the pathogenic Mycobacterium tuberculosis). The unphosphorylated form of OdhI inhibits the OdhA protein, a key enzyme of the TCA cycle, whereas the phosphorylated form is inactive. OdhI is predicted to be mainly a single FHA domain, a module that mediates protein-protein interaction through binding of phosphothreonine peptides, with a disordered N-terminal extension substrate of the serine/threonine protein kinases. In this study, we solved the solution structure of the unphosphorylated and phosphorylated isoforms of the protein. We observed a major conformational change between the two forms characterized by the binding of the phosphorylated N-terminal part of the protein to its own FHA domain, consequently inhibiting it. This structural observation corresponds to a new autoinhibition mechanism described for a FHA domain protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Binding Sites / genetics
  • Corynebacterium glutamicum / enzymology
  • Corynebacterium glutamicum / genetics
  • Corynebacterium glutamicum / metabolism
  • Enzyme Inhibitors / metabolism*
  • Ketoglutarate Dehydrogenase Complex / antagonists & inhibitors*
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Weight
  • Mycobacterium tuberculosis / enzymology
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / metabolism
  • Peptides / chemistry
  • Peptides / metabolism
  • Phosphorylation
  • Phosphothreonine / chemistry
  • Phosphothreonine / metabolism
  • Protein Binding / genetics
  • Protein Conformation
  • Protein Structure, Tertiary / genetics
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Sequence Homology, Amino Acid
  • Substrate Specificity / genetics


  • Bacterial Proteins
  • Enzyme Inhibitors
  • Peptides
  • Phosphothreonine
  • Ketoglutarate Dehydrogenase Complex
  • Protein-Serine-Threonine Kinases