Conserved YjgF protein family deaminates reactive enamine/imine intermediates of pyridoxal 5'-phosphate (PLP)-dependent enzyme reactions

J Biol Chem. 2012 Jan 27;287(5):3454-61. doi: 10.1074/jbc.M111.304477. Epub 2011 Nov 17.

Abstract

The YjgF/YER057c/UK114 family of proteins is conserved in all domains of life, suggesting that the role of these proteins arose early and was maintained throughout evolution. Metabolic consequences of lacking this protein in Salmonella enterica and other organisms have been described, but the biochemical function of YjgF remained unknown. This work provides the first description of a conserved biochemical activity for the YjgF protein family. Our data support the conclusion that YjgF proteins have enamine/imine deaminase activity and accelerate the release of ammonia from reactive enamine/imine intermediates of the pyridoxal 5'-phosphate-dependent threonine dehydratase (IlvA). Results from structure-guided mutagenesis experiments suggest that YjgF lacks a catalytic residue and that it facilitates ammonia release by positioning a critical water molecule in the active site. YjgF is renamed RidA (reactive intermediate/imine deaminase A) to reflect the conserved activity of the protein family described here. This study, combined with previous physiological studies on yjgF mutants, suggests that intermediates of pyridoxal 5'-phosphate-mediated reactions may have metabolic consequences in vivo that were previously unappreciated. The conservation of the RidA/YjgF family suggests that reactive enamine/imine metabolites are of concern to all organisms.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aminohydrolases / chemistry
  • Aminohydrolases / genetics
  • Aminohydrolases / metabolism*
  • Archaeal Proteins / chemistry
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism*
  • Bacillus subtilis / enzymology*
  • Bacillus subtilis / genetics
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Imines / chemistry
  • Imines / metabolism*
  • Pyridoxal Phosphate / chemistry
  • Pyridoxal Phosphate / metabolism*
  • Pyrococcus furiosus / enzymology*
  • Pyrococcus furiosus / genetics
  • Salmonella enterica / enzymology
  • Salmonella enterica / genetics

Substances

  • Archaeal Proteins
  • Bacterial Proteins
  • Imines
  • Pyridoxal Phosphate
  • Aminohydrolases