Structure and catalytic mechanism of a novel N-succinyl-L-ornithine transcarbamylase in arginine biosynthesis of Bacteroides fragilis

J Biol Chem. 2006 Jul 21;281(29):20623-31. doi: 10.1074/jbc.M601229200. Epub 2006 May 16.

Abstract

A Bacteroides fragilis gene (argF'(bf)), the disruption of which renders the bacterium auxotrophic for arginine, was expressed and its recombinant protein purified and studied. The novel protein catalyzes the carbamylation of N-succinyl-L-ornithine but not L-ornithine or N-acetyl-L-ornithine, forming N-succinyl-L-citrulline. Crystal structures of this novel transcarbamylase complexed with carbamyl phosphate and N-succinyl-L-norvaline, as well as sulfate and N-succinyl-L-norvaline have been determined and refined to 2.9 and 2.8 A resolution, respectively. They provide structural evidence that this protein is a novel N-succinyl-L-ornithine transcarbamylase. The data provided herein suggest that B. fragilis uses N-succinyl-L-ornithine rather than N-acetyl-L-ornithine for de novo arginine biosynthesis and therefore that this pathway in Bacteroides is different from the canonical arginine biosynthetic pathway of most organisms. Comparison of the structures of the new protein with those recently reported for N-acetyl-L-ornithine transcarbamylase indicates that amino acid residue 90 (B. fragilis numbering) plays an important role in conferring substrate specificity for N-succinyl-L-ornithine versus N-acetyl-L-ornithine. Movement of the 120 loop upon substrate binding occurs in N-succinyl-L-ornithine transcarbamylase, while movement of the 80 loop and significant domain closure take place as in other transcarbamylases. These findings provide new information on the putative role of succinylated intermediates in arginine biosynthesis and on the evolution of transcarbamylases.

Publication types

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

MeSH terms

  • Acyltransferases / chemistry*
  • Acyltransferases / genetics
  • Acyltransferases / metabolism*
  • Amino Acid Sequence
  • Amino Acids / analysis
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Bacteroides fragilis / enzymology*
  • Binding Sites
  • Conserved Sequence
  • DNA Primers
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • Amino Acids
  • Bacterial Proteins
  • DNA Primers
  • Recombinant Proteins
  • Acyltransferases
  • arginine succinyltransferase

Associated data

  • PDB/2FG6
  • PDB/2FG7