Structure of activated aconitase: formation of the [4Fe-4S] cluster in the crystal

Proc Natl Acad Sci U S A. 1989 May;86(10):3639-43. doi: 10.1073/pnas.86.10.3639.


The structure of activated pig heart aconitase [citrate(isocitrate) hydro-lyase, EC] containing a [4Fe-4S] cluster has been refined at 2.5-A resolution to a crystallographic residual of 18.2%. Comparison of this structure to the recently determined 2.1-A resolution structure of the inactive enzyme containing a [3Fe-4S] cluster, by difference Fourier analysis, shows that upon activation iron is inserted into the structure isomorphously. The common atoms of the [3Fe-4S] and [4Fe-4S] cores agree within 0.1 A; the three common cysteinyl S gamma ligand atoms agree within 0.25 A. The fourth ligand of the Fe inserted into the [3Fe-4S] cluster is a water or hydroxyl from solvent, consistent with the absence of a free cysteine ligand in the enzyme active site cleft and the isomorphism of the two structures. A water molecule occupies a similar site in the crystal structure of the inactive enzyme.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aconitate Hydratase*
  • Animals
  • Binding Sites
  • Enzyme Activation
  • Iron-Sulfur Proteins / ultrastructure*
  • Metalloproteins / ultrastructure*
  • Models, Molecular
  • Myocardium / enzymology
  • Protein Conformation
  • Swine
  • X-Ray Diffraction


  • Iron-Sulfur Proteins
  • Metalloproteins
  • Aconitate Hydratase