title: Crystal structure of Aeromonas proteolytica aminopeptidase: a prototypical member of the co-catalytic zinc enzyme family.
abstract: BACKGROUND
  Aminopeptidases specifically cleave the amino-terminal residue from polypeptide chains and are involved in the metabolism of biologically active peptides. The family includes zinc-dependent enzymes possessing either one or two zinc ions per active site. Structural studies providing a detailed view of the metal environment may reveal whether the one-zinc and two-zinc enzymes constitute structurally and mechanistically distinct subclasses, and what role the metal ions play in the catalytic process.
  
  
  RESULTS
  We have solved the crystal structure of the monomeric aminopeptidase from Aeromonas proteolytica at 1.8 A resolution. The protein is folded into a single alpha/beta globular domain. The active site contains two zinc ions (3.5 A apart) with shared ligands and symmetrical coordination spheres. We have compared it with the related bovine lens leucine aminopeptidase and the cobalt-containing Escherichia coli methionine aminopeptidase.
  
  
  CONCLUSIONS
  The environment and coordination of the two zinc ions in A. proteolytica aminopeptidase strongly support the view that the two metal ions constitute a co-catalytic unit and play equivalent roles during catalysis. This conflicts with the conclusions drawn from the related bovine leucine aminopeptidase and early biochemical studies. In addition, the known specificity of the aminopeptidase for hydrophobic amino-terminal residues is reflected in the hydrophobicity of the active site cleft.
authors.affiliation: Laboratoire de Biologie Structurale, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors.forename: B
authors.initials: B
authors.lastname: Chevrier
authors.forename: C
authors.initials: C
authors.lastname: Schalk
authors.forename: H
authors.initials: H
authors.lastname: D'Orchymont
authors.forename: J M
authors.initials: JM
authors.lastname: Rondeau
authors.forename: D
authors.initials: D
authors.lastname: Moras
authors.forename: C
authors.initials: C
authors.lastname: Tarnus
mesh_terms: D000333:Aeromonas / Q000201:enzymology*; D000495:Allosteric Site; D000626:Aminopeptidases / Q000737:chemistry*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D002417:Cattle; D018360:Crystallography, X-Ray; D005136:Eye Proteins / Q000737:chemistry; D007931:Leucyl Aminopeptidase / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D015032:Zinc
chemical_list: D001426:Bacterial Proteins; D005136:Eye Proteins; D000626:Aminopeptidases; D007931:Leucyl Aminopeptidase; D015032:Zinc