Alternating arginine-modulated substrate specificity in an engineered tyrosine aminotransferase

Nat Struct Biol. 1995 Jul;2(7):548-53. doi: 10.1038/nsb0795-548.


Mutation of six residues of Escherichia coli aspartate aminotransferase results in substantial acquisition of the transamination properties of tyrosine amino-transferase without loss of aspartate transaminase activity. X-ray crystallographic analysis of key inhibitor complexes of the hexamutant reveals the structural basis for this substrate selectivity. It appears that tyrosine aminotransferase achieves nearly equal affinities for a wide range of amino acids by an unusual conformational switch. An active-site arginine residue either shifts its position to electrostatically interact with charged substrates or moves aside to allow access of aromatic ligands.

Publication types

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

MeSH terms

  • Arginine
  • Aspartate Aminotransferases / metabolism*
  • Binding Sites
  • Crystallography, X-Ray
  • Escherichia coli / enzymology
  • Ligands
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Conformation
  • Structure-Activity Relationship
  • Substrate Specificity
  • Tyrosine Transaminase / metabolism*


  • Ligands
  • Arginine
  • Aspartate Aminotransferases
  • Tyrosine Transaminase