title: Transition metal ions induce carnosinase activity in PepD-homologous protein from Porphyromonas gingivalis.
abstract: Aminoacylhistidine dipeptidase (EC 3.4.13.3; also Xaa-His dipeptidase, carnosinase, or PepD) catalyzes the cleavage and release of an N-terminal amino acid, which is usually a neutral or hydrophobic residue, from an Xaa-His dipeptide or degraded peptide fragment. PepD enzyme is found extensively in prokaryotes and eukaryotes, and belongs to the metallopeptidase family M20, a part of the metallopeptidase H (MH) clan. Carnosine is a naturally occurring dipeptide (β-alanyl-l-histidine) present in mammalian tissues that has protective functions in addition to anti-oxidant and free-radical scavenging roles. During bacterial infections, degradation of l-carnosine via carnosinase or PepD-like enzymes may enhance the destructive potential of bacteria, resulting in a pathological impact. This process has been proposed to act in an anti-oxidant manner in vivo. In the present study, the recombinant PepD protein encoded by Porphyromonas gingivalis TDC60 pepD was generated and biochemically characterized. In addition, a recombinant dipeptidase enzyme was found to function not only as an alanine-aminopeptidase, but also as a carnosinase. Furthermore, when carnosine was used as substrate for PepD, the transition metals, Mn(2+), Fe(2+), Co(2+), and Ni(2+) stimulated the hydrolyzing activity of rPepD with β-alanine and l-histidine. Based on its metal ion specificity, we propose that this enzyme should not only be termed l-aminopeptidase, but also a carnosinase.
authors: Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, 2-870-1, Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan. maak08017@g.nihon-u.ac.jp
authors: Akinobu
authors: A
authors: Aoki
authors: Yasuko
authors: Y
authors: Shibata
authors: Soichiro
authors: S
authors: Okano
authors: Fumito
authors: F
authors: Maruyama
authors: Atsuo
authors: A
authors: Amano
authors: Ichiro
authors: I
authors: Nakagawa
authors: Yoshimitsu
authors: Y
authors: Abiko
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002336:Carnosine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004150:Dipeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D016966:Porphyromonas gingivalis / Q000737:chemistry / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D008670:Metals; D002336:Carnosine; D004150:Dipeptidases; C019673:aminoacyl-histidine dipeptidase