High-resolution structure of ybfF from Escherichia coli K12: a unique substrate-binding crevice generated by domain arrangement

J Mol Biol. 2008 Mar 7;376(5):1426-37. doi: 10.1016/j.jmb.2007.12.062. Epub 2008 Jan 4.


Esterases are one of the most common enzymes and are involved in diverse cellular functions. ybfF protein from Escherichia coli (Ec_ybfF) belongs to the esterase family for the large substrates, palmitoyl coenzyme A and malonyl coenzyme A, which are important cellular intermediates for energy conversion and biomolecular synthesis. To obtain molecular information on ybfF esterase, which is found in a wide range of microorganisms, we elucidated the crystal structures of Ec_ybfF in complexes with small molecules at resolutions of 1.1 and 1.68 A, respectively. The structure of Ec_ybfF is composed of a globular alpha/beta hydrolase domain with a three-helical bundle cap, which is linked by a kinked helix to the alpha/beta hydrolase domain. It contains a catalytic tetrad of Ser-His-Asp-Ser with the first Ser acting as a nucleophile. The unique spatial arrangement and orientation of the helical cap with respect to the alpha/beta hydrolase domain form a substrate-binding crevice for large substrates. The helical cap is also directly involved in catalysis by providing a substrate anchor, viz., the conserved residues of Arg123 and Tyr208. The high-resolution structure of Ec_ybfF shows that the inserted helical bundle structure and its spatial orientation with respect to the alpha/beta hydrolase domain are critical for creating a large inner space and constituting a specific active site, thereby providing the broad substrate spectrum toward large biomolecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Escherichia coli K12 / chemistry*
  • Escherichia coli Proteins / chemistry*
  • Esterases / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Sequence Alignment


  • Escherichia coli Proteins
  • Esterases
  • ybfF protein, E coli

Associated data

  • PDB/3BF7
  • PDB/3BF8