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Exopeptidases and gingipains in Porphyromonas gingivalis as prerequisites for its amino acid metabolism

View Article: PubMed Central - PubMed

ABSTRACT

Porphyromonas gingivalis, an asaccharolytic bacterium, utilizes amino acids as energy and carbon sources. Since amino acids are incorporated into the bacterial cells mainly as di- and tri-peptides, exopeptidases including dipeptidyl-peptidase (DPP) and tripeptidyl-peptidase are considered to be prerequisite components for their metabolism. We recently discovered DPP11, DPP5, and acylpeptidyl oligopeptidase in addition to previously reported DPP4, DPP7, and prolyl tripeptidyl peptidase A. DPP11 is a novel enzyme specific for acidic P1 residues (Asp and Glu) and distributed ubiquitously in eubacteria, while DPP5 is preferential for the hydrophobic P1 residue and the first entity identified in prokaryotes. Recently, acylpeptidyl oligopeptidase with a preference for hydrophobic P1 residues was found to release N-terminally blocked di- and tri-peptides. Furthermore, we also demonstrated that gingipains R and K contribute to P1-basic dipeptide production. These observations implicate that most, if not all, combinations of di- and tri-peptides are produced from extracellular oligopeptides even with an N-terminal modification. Here, we review P. gingivalis exopeptidases mainly in regard to their enzymatic characteristics. These exopeptidases with various substrate specificities benefit P. gingivalis for obtaining energy and carbon sources from the nutritionally limited subgingival environment.

No MeSH data available.


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Schematic illustration of extracellular oligopeptide metabolism in P. gingivalis. The metabolic pathway of P. gingivalis from the extracellular polypeptides, di- and tri-peptide incorporation, amino acid metabolism, and excretion as short-chain fatty acids, are schematically illustrated [10], [15]. Amino acids, except for Ser and Thr, are mainly transported as di- and tri-peptides via oligopeptide transporters [10]. Rgp and Kgp are mainly localized on the outer membrane (OM), while DPPs, PtpA, and AOP are located in periplasmic space [23], [24], [25]. Scissors indicate peptidases, which cleave peptide bonds at specific positions. Stars represent acylaminoacyl groups at the N-terminus. IM, inner membrane.
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fig0005: Schematic illustration of extracellular oligopeptide metabolism in P. gingivalis. The metabolic pathway of P. gingivalis from the extracellular polypeptides, di- and tri-peptide incorporation, amino acid metabolism, and excretion as short-chain fatty acids, are schematically illustrated [10], [15]. Amino acids, except for Ser and Thr, are mainly transported as di- and tri-peptides via oligopeptide transporters [10]. Rgp and Kgp are mainly localized on the outer membrane (OM), while DPPs, PtpA, and AOP are located in periplasmic space [23], [24], [25]. Scissors indicate peptidases, which cleave peptide bonds at specific positions. Stars represent acylaminoacyl groups at the N-terminus. IM, inner membrane.

Mentions: Initially, DPP4, DPP7, and prolyl tripeptidyl peptidase A (PtpA) were the only exopeptidases identified in P. gingivalis. These share substrates according to their altered specificities, as DPP4 is highly specific for Pro at the penultimate position from the N-terminus (P1 position), though it accepts Ala to a lesser extent [18], [19], DPP7 is preferential to P1 hydrophobic amino acids [20], and PtpA liberates tripeptides with P1-position Pro, an activity that is able to compensate DPP4 and DPP7, which are unable to accept oligopeptides with Pro at the third position [21]. Although these three exopeptidases could not sufficiently explain the entire metabolism of extracellular oligopeptides, no other members were added to the list of P. gingivalis exopeptidases for a period of 10 years. Even though Asp and Glu are located in central routes of metabolism in P. gingivalis[10], [15], [22] (Fig. 1), oligopeptides with acidic amino acid residues do not seem to be efficiently produced. Moreover, none of DPPs [19], [21], [23] and PtpA [20] are incapable of utilizing N-terminally blocked polypeptides, such as the various serum proteins present in gingival crevicular fluid.


Exopeptidases and gingipains in Porphyromonas gingivalis as prerequisites for its amino acid metabolism
Schematic illustration of extracellular oligopeptide metabolism in P. gingivalis. The metabolic pathway of P. gingivalis from the extracellular polypeptides, di- and tri-peptide incorporation, amino acid metabolism, and excretion as short-chain fatty acids, are schematically illustrated [10], [15]. Amino acids, except for Ser and Thr, are mainly transported as di- and tri-peptides via oligopeptide transporters [10]. Rgp and Kgp are mainly localized on the outer membrane (OM), while DPPs, PtpA, and AOP are located in periplasmic space [23], [24], [25]. Scissors indicate peptidases, which cleave peptide bonds at specific positions. Stars represent acylaminoacyl groups at the N-terminus. IM, inner membrane.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382784&req=5

fig0005: Schematic illustration of extracellular oligopeptide metabolism in P. gingivalis. The metabolic pathway of P. gingivalis from the extracellular polypeptides, di- and tri-peptide incorporation, amino acid metabolism, and excretion as short-chain fatty acids, are schematically illustrated [10], [15]. Amino acids, except for Ser and Thr, are mainly transported as di- and tri-peptides via oligopeptide transporters [10]. Rgp and Kgp are mainly localized on the outer membrane (OM), while DPPs, PtpA, and AOP are located in periplasmic space [23], [24], [25]. Scissors indicate peptidases, which cleave peptide bonds at specific positions. Stars represent acylaminoacyl groups at the N-terminus. IM, inner membrane.
Mentions: Initially, DPP4, DPP7, and prolyl tripeptidyl peptidase A (PtpA) were the only exopeptidases identified in P. gingivalis. These share substrates according to their altered specificities, as DPP4 is highly specific for Pro at the penultimate position from the N-terminus (P1 position), though it accepts Ala to a lesser extent [18], [19], DPP7 is preferential to P1 hydrophobic amino acids [20], and PtpA liberates tripeptides with P1-position Pro, an activity that is able to compensate DPP4 and DPP7, which are unable to accept oligopeptides with Pro at the third position [21]. Although these three exopeptidases could not sufficiently explain the entire metabolism of extracellular oligopeptides, no other members were added to the list of P. gingivalis exopeptidases for a period of 10 years. Even though Asp and Glu are located in central routes of metabolism in P. gingivalis[10], [15], [22] (Fig. 1), oligopeptides with acidic amino acid residues do not seem to be efficiently produced. Moreover, none of DPPs [19], [21], [23] and PtpA [20] are incapable of utilizing N-terminally blocked polypeptides, such as the various serum proteins present in gingival crevicular fluid.

View Article: PubMed Central - PubMed

ABSTRACT

Porphyromonas gingivalis, an asaccharolytic bacterium, utilizes amino acids as energy and carbon sources. Since amino acids are incorporated into the bacterial cells mainly as di- and tri-peptides, exopeptidases including dipeptidyl-peptidase (DPP) and tripeptidyl-peptidase are considered to be prerequisite components for their metabolism. We recently discovered DPP11, DPP5, and acylpeptidyl oligopeptidase in addition to previously reported DPP4, DPP7, and prolyl tripeptidyl peptidase A. DPP11 is a novel enzyme specific for acidic P1 residues (Asp and Glu) and distributed ubiquitously in eubacteria, while DPP5 is preferential for the hydrophobic P1 residue and the first entity identified in prokaryotes. Recently, acylpeptidyl oligopeptidase with a preference for hydrophobic P1 residues was found to release N-terminally blocked di- and tri-peptides. Furthermore, we also demonstrated that gingipains R and K contribute to P1-basic dipeptide production. These observations implicate that most, if not all, combinations of di- and tri-peptides are produced from extracellular oligopeptides even with an N-terminal modification. Here, we review P. gingivalis exopeptidases mainly in regard to their enzymatic characteristics. These exopeptidases with various substrate specificities benefit P. gingivalis for obtaining energy and carbon sources from the nutritionally limited subgingival environment.

No MeSH data available.


Related in: MedlinePlus