Molecular characterization of novel pyridoxal-5'-phosphate-dependent enzymes from the human microbiome

Protein Sci. 2014 Aug;23(8):1060-76. doi: 10.1002/pro.2493. Epub 2014 Jun 14.

Abstract

Pyridoxal-5'-phosphate or PLP, the active form of vitamin B6, is a highly versatile cofactor that participates in a large number of mechanistically diverse enzymatic reactions in basic metabolism. PLP-dependent enzymes account for ∼1.5% of most prokaryotic genomes and are estimated to be involved in ∼4% of all catalytic reactions, making this an important class of enzymes. Here, we structurally and functionally characterize three novel PLP-dependent enzymes from bacteria in the human microbiome: two are from Eubacterium rectale, a dominant, nonpathogenic, fecal, Gram-positive bacteria, and the third is from Porphyromonas gingivalis, which plays a major role in human periodontal disease. All adopt the Type I PLP-dependent enzyme fold and structure-guided biochemical analysis enabled functional assignments as tryptophan, aromatic, and probable phosphoserine aminotransferases.

Keywords: PLP-dependent enzymes; Protein Structure Initiative; biochemical characterization; crystal structure; human microbiome; structural genomics.

Publication types

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

MeSH terms

  • Crystallography, X-Ray
  • Eubacterium / enzymology*
  • Humans
  • Microbiota*
  • Models, Molecular
  • Oxidoreductases / chemistry
  • Oxidoreductases / metabolism*
  • Porphyromonas gingivalis / enzymology*
  • Protein Conformation
  • Pyridoxal Phosphate / chemistry
  • Pyridoxal Phosphate / metabolism*
  • Transaminases / chemistry
  • Transaminases / metabolism*

Substances

  • Pyridoxal Phosphate
  • Oxidoreductases
  • Transaminases

Associated data

  • PDB/1BW0
  • PDB/1GDE
  • PDB/1VP4
  • PDB/1ay4
  • PDB/2GB3
  • PDB/3bwn
  • PDB/3bwo
  • PDB/3ele
  • PDB/3f0h
  • PDB/3g0t