title: Enzymatic degradation of beta- and mixed alpha,beta-oligopeptides.
abstract: One of the main and most astonishing characteristics of peptides comprised of beta-amino acids with proteinogenic side chains is their extraordinarily high stability towards enzymatic degradation. So far, only certain microbial enzymes have been shown to cleave N-terminal beta(3)-homoamino acid residues from peptides. In this work, the L-aminopeptidase-D-amidase/esterase (DmpA) from Ochrobactrum anthropi LMG7991 is compared to two closely related beta-peptidyl aminopeptidases (BapA), which originate from Sphingosinicella strains, and to microsomal leucine aminopeptidase (LAP) as a reference. All four enzymes are aminopeptidases cleaving N-terminal amino acids from small peptides. Degradation experiments reveal that DmpA and both BapA enzymes exhibit unique, but clearly distinct substrate specificities and preferences. DmpA also cleaves beta- and mixed alpha,beta-peptides and amides, but a short side chain of the N-terminal beta-amino acid residue seems to be a prerequisite, since only peptides carrying N-terminal betahGly and beta(3)hAla are hydrolyzed with good efficiencies. Both beta-peptidyl aminopeptidases cleave beta-amino acids from a variety of beta-peptides and mixed alpha,beta-peptides, but they do not accept alpha-amino acids in the N-terminal position. Astonishingly, DmpA exhibited much higher catalytical rates for the mixed dipeptide carnosine (H-betahGly-His-OH) than for any other substrate described until now.
authors.affiliation: Eawag, Swiss Federal Institute of Aquatic Science and Technology, CH-8600 Dübendorf.
authors.forename: Tobias
authors.initials: T
authors.lastname: Heck
authors.forename: Michael
authors.initials: M
authors.lastname: Limbach
authors.forename: Birgit
authors.initials: B
authors.lastname: Geueke
authors.forename: Martin
authors.initials: M
authors.lastname: Zacharias
authors.forename: James
authors.initials: J
authors.lastname: Gardiner
authors.forename: Hans-Peter E
authors.initials: HP
authors.lastname: Kohler
authors.forename: Dieter
authors.initials: D
authors.lastname: Seebach
mesh_terms: D000626:Aminopeptidases / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D002336:Carnosine / Q000737:chemistry; D002384:Catalysis; D007700:Kinetics; D007931:Leucyl Aminopeptidase / Q000737:chemistry; D013058:Mass Spectrometry; D008956:Models, Chemical; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; C475954:BapA protein, Borrelia burgdorferi; D009842:Oligopeptides; D010455:Peptides; D002336:Carnosine; D000626:Aminopeptidases; D007931:Leucyl Aminopeptidase; C118321:DmpA protein, Ochrobactrum anthropi