Lysine and arginine biosyntheses mediated by a common carrier protein in Sulfolobus

Nat Chem Biol. 2013 Apr;9(4):277-83. doi: 10.1038/nchembio.1200. Epub 2013 Feb 24.


LysW has been identified as a carrier protein in the lysine biosynthetic pathway that is active through the conversion of α-aminoadipate (AAA) to lysine. In this study, we found that the hyperthermophilic archaeon, Sulfolobus acidocaldarius, not only biosynthesizes lysine through LysW-mediated protection of AAA but also uses LysW to protect the amino group of glutamate in arginine biosynthesis. In this archaeon, after LysW modification, AAA and glutamate are converted to lysine and ornithine, respectively, by a single set of enzymes with dual functions. The crystal structure of ArgX, the enzyme responsible for modification and protection of the amino moiety of glutamate with LysW, was determined in complex with LysW. Structural comparison and enzymatic characterization using Sulfolobus LysX, Sulfolobus ArgX and Thermus LysX identify the amino acid motif responsible for substrate discrimination between AAA and glutamate. Phylogenetic analysis reveals that gene duplication events at different stages of evolution led to ArgX and LysX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Aminoadipic Acid / metabolism
  • Archaeal Proteins / chemistry
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism*
  • Arginine / biosynthesis*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Catalytic Domain
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Evolution, Molecular
  • Gene Duplication
  • Glutamic Acid / metabolism
  • Lysine / biosynthesis*
  • Models, Molecular
  • Ornithine / metabolism
  • Phylogeny
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Substrate Specificity
  • Sulfolobus acidocaldarius / genetics
  • Sulfolobus acidocaldarius / metabolism*
  • Thermus / genetics
  • Thermus / metabolism


  • Archaeal Proteins
  • Bacterial Proteins
  • Carrier Proteins
  • Recombinant Proteins
  • 2-Aminoadipic Acid
  • Glutamic Acid
  • Arginine
  • Ornithine
  • Lysine

Associated data

  • PDB/3VPB
  • PDB/3VPC
  • PDB/3VPD