Structural basis of the induced-fit mechanism of 1,4-dihydroxy-2-naphthoyl coenzyme A synthase from the crotonase fold superfamily

PLoS One. 2013 Apr 26;8(4):e63095. doi: 10.1371/journal.pone.0063095. Print 2013.


1, 4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase is a typical crotonase fold enzyme with an implicated role of conformational changes in catalysis. We have identified these conformational changes by determining the structures of its Escherichia coli and Synechocystis sp. PCC6803 orthologues in complex with a product analog. The structural changes include the folding of an active-site loop into a β-hairpin and significant reorientation of a helix at the carboxy terminus. Interestingly, a new interface is formed between the ordered loop and the reoriented helix, both of which also form additional interactions with the coenzyme A moiety of the ligand. Site-directed mutation of the amino acid residues involved in these ligand-induced interactions significantly diminishes the enzyme activity. These results suggest a catalytically essential induced-fit that is likely initiated by the enzyme-ligand interactions at the active site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain
  • Crystallography, X-Ray
  • Escherichia coli / chemistry*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Ligands
  • Models, Molecular*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oxo-Acid-Lyases / chemistry*
  • Oxo-Acid-Lyases / genetics
  • Oxo-Acid-Lyases / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Structural Homology, Protein
  • Synechocystis / chemistry*
  • Synechocystis / enzymology
  • Synechocystis / genetics
  • Vitamin K 2 / chemistry*
  • Vitamin K 2 / metabolism


  • Escherichia coli Proteins
  • Ligands
  • Recombinant Proteins
  • Vitamin K 2
  • 1,4-dihydroxy-2-naphthoyl-CoA synthase, E coli
  • Oxo-Acid-Lyases

Grants and funding

This work was supported in part by GRF601209 and RPC11SC16 from the Research Grants Council of the HKSAR government (to Z.G.) and 2009CB918600 from the National Program on Key Basic Research of China (to J.Z.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.