Crystal structure of lipoate-protein ligase A from Escherichia coli. Determination of the lipoic acid-binding site

J Biol Chem. 2005 Sep 30;280(39):33645-51. doi: 10.1074/jbc.M505010200. Epub 2005 Jul 25.


Lipoate-protein ligase A (LplA) catalyzes the formation of lipoyl-AMP from lipoate and ATP and then transfers the lipoyl moiety to a specific lysine residue on the acyltransferase subunit of alpha-ketoacid dehydrogenase complexes and on H-protein of the glycine cleavage system. The lypoyllysine arm plays a pivotal role in the complexes by shuttling the reaction intermediate and reducing equivalents between the active sites of the components of the complexes. We have determined the X-ray crystal structures of Escherichia coli LplA alone and in a complex with lipoic acid at 2.4 and 2.9 angstroms resolution, respectively. The structure of LplA consists of a large N-terminal domain and a small C-terminal domain. The structure identifies the substrate binding pocket at the interface between the two domains. Lipoic acid is bound in a hydrophobic cavity in the N-terminal domain through hydrophobic interactions and a weak hydrogen bond between carboxyl group of lipoic acid and the Ser-72 or Arg-140 residue of LplA. No large conformational change was observed in the main chain structure upon the binding of lipoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Conserved Sequence
  • Crystallography, X-Ray*
  • Escherichia coli / chemistry
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism*
  • Hydrogen Bonding
  • Kinetics
  • Ligases / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Spectrum Analysis, Raman
  • Thioctic Acid / chemistry
  • Thioctic Acid / genetics
  • Thioctic Acid / metabolism*


  • Escherichia coli Proteins
  • Thioctic Acid
  • Ligases

Associated data

  • PDB/1X2G
  • PDB/1X2H