The DmpA aminopeptidase from Ochrobactrum anthropi LMG7991 is the prototype of a new terminal nucleophile hydrolase family

Biochem J. 1999 Jul 1;341 ( Pt 1)(Pt 1):147-55.

Abstract

The DmpA (d-aminopeptidase A) protein produced by Ochrobactrum anthropi hydrolyses p-nitroanilide derivatives of glycine and d-alanine more efficiently than that of l-alanine. When regular peptides are utilized as substrates, the enzyme behaves as an aminopeptidase with a preference for N-terminal residues in an l configuration, thus exemplifying an interesting case of stereospecificity reversal. The best-hydrolysed substrate is l-Ala-Gly-Gly, but tetra- and penta-peptides are also efficiently hydrolysed. The gene encodes a 375-residue precursor, but the active enzyme contains two polypeptides corresponding to residues 2-249 (alpha-subunit) and 250-375 (beta-subunit) of the precursor. Residues 249 and 250 are a Gly and a Ser respectively, and various substitutions performed by site-directed mutagenesis result in the production of an uncleaved and inactive protein. The N-terminal Ser residue of the beta-subunit is followed by a hydrophobic peptide, which is predicted to form a beta-strand structure. All these properties strongly suggest that DmpA is an N-terminal amidohydrolase. An exploration of the databases highlights the presence of a number of open reading frames encoding related proteins in various bacterial genomes. Thus DmpA is very probably the prototype of an original family of N-terminal hydrolases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / classification*
  • Amidohydrolases / genetics
  • Amidohydrolases / metabolism
  • Amino Acid Sequence
  • Aminopeptidases / classification*
  • Aminopeptidases / genetics
  • Aminopeptidases / metabolism
  • Bacterial Proteins*
  • Dipeptides / metabolism
  • Enzyme Activation
  • Gram-Negative Bacteria / enzymology*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oligopeptides / metabolism
  • Protein Precursors / classification*
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Recombinant Proteins
  • Substrate Specificity

Substances

  • Bacterial Proteins
  • Dipeptides
  • Oligopeptides
  • Protein Precursors
  • Recombinant Proteins
  • Aminopeptidases
  • DmpA protein, Ochrobactrum anthropi
  • Amidohydrolases