title: Bacterial β-aminopeptidases: structural insights and applications for biocatalysis.
abstract: β-Aminopeptidases comprise a class of enzymes with functional and structural similarities. All members of the β-aminopeptidases described to date were isolated from bacterial sources. Uniquely, they catalyze the hydrolysis of β(3) - and/or β(2) -amino acid residues from amides and peptides that are otherwise considered proteolytically stable. Due to this unusual reactivity with β-peptide substrates, β-aminopeptidases have potential to be used as biocatalysts for β-peptide synthesis and for the resolution of enantiomerically pure β-amino acids from racemic substrate mixtures. β-Aminopeptidases are formed from an inactive precursor by posttranslational autoproteolytic cleavage, exposing the catalytic nucleophile at the N-terminus of the newly formed β-polypeptide chain. Such an activation step is a characteristic trait of enzymes of the N-terminal nucleophile (Ntn) hydrolase superfamily. However, classical Ntn hydrolases and β-aminopeptidases differ by the fold of their catalytic cores and are hence likely to originate from distinct evolutionary ancestors. In this contribution, we review the existing literature on β-aminopeptidases, including biochemical and functional studies, as well as structural investigations that recently allowed insights into the catalytic mechanisms of precursor processing and β-peptide conversion.
authors.affiliation: EMPA, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Biomaterials, Lerchenfeldstrasse 5, CH-9014 St. Gallen, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Heck
authors.forename: Birgit
authors.initials: B
authors.lastname: Geueke
authors.forename: Hans-Peter E
authors.initials: HP
authors.lastname: Kohler
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000626:Aminopeptidases / Q000737:chemistry* / Q000378:metabolism; D001419:Bacteria / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D000596:Amino Acids; D010455:Peptides; D000626:Aminopeptidases; D000581:Amidohydrolases; C438834:N-terminal nucleophile hydrolase