Dipeptidyl-Peptidase III

Barrett, Alan J.

doi:10.1016/b978-0-12-382219-2.00289-1

Cited by 5 publications

(10 citation statements)

References 36 publications

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“…In addition to above three DPPs, the gene (PGN_1645) encoding putative DPPIII (YP_004510152.1) has been found in P. gingivalis ATCC 33277 [19]. Although DPPIII has been considered to exclusively exist in eukaryotes [20], bacterial DPPIII has recently reported in Bacteroides thetaiotaomicron [21]. B. thetaiotaomicron DPPIII most potently hydrolyzes Arg‐Arg‐2‐naphthylamide as does eukaryotic DPPIII [20].…”

Section: Introductionmentioning

confidence: 99%

“…Although DPPIII has been considered to exclusively exist in eukaryotes [20], bacterial DPPIII has recently reported in Bacteroides thetaiotaomicron [21]. B. thetaiotaomicron DPPIII most potently hydrolyzes Arg‐Arg‐2‐naphthylamide as does eukaryotic DPPIII [20]. However, its N‐terminal sequence indicates its localization in the cytosol [21], and hence, bacterial DPPIII may not participate in the degradation of environmental peptides, but be responsible for degradation of cytosolic substrates.…”

Section: Introductionmentioning

confidence: 99%

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Phenylalanine 664 of dipeptidyl peptidase (DPP) 7 and Phenylalanine 671 of DPP11 mediate preference for P2‐position hydrophobic residues of a substrate

et al. 2013

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Dipeptidyl peptidases (DPPs) are crucial for the energy metabolism in Porphyromonas gingivalis, a Gram-negative proteolytic and asaccharolytic anaerobic rod causing chronic periodontitis. Three DPPs, DPPIV specific for Pro, DPP7 for hydrophobic residues and DPP11 for Asp/Glu at the P1 position, are expressed in the bacterium. Like DPP7, DPP11 belongs to the S46 protease family, and they share 38.7% sequence identity. Although DPP11 is preferential for hydrophobic residues at the P2 position, it has been reported that DPP7 has no preference at the P2 position. In the present study, we defined the detailed P2 substrate preference of DPP7 and the amino acid residue responsible for the specificity. DPP7 most efficiently hydrolyzed Met-Leu-dipeptidyl-4-methylcoumaryl-7-amide (MCA) carrying hydrophobic residues at the P1 position with kcat/Km of 10.62 ± 2.51 μM−1 s−1, while it unexpectedly cleaved substrates with hydrophilic (Gln, Asn) or charged (Asp, Arg) residues. Examination with 21 dipeptidyl MCA demonstrated that DPP7-peptidase activity was dependent on hydrophobicity of the P2- as well as P1-position residue, thus it correlated best with the sum of the hydrophobicity index of P1- and P2-amino acid residues. Hydrophobicity of the P1 and P2 positions ensured efficient enzyme catalysis by increasing kcat and lowering Km values, respectively. Substitution of hydrophobic residues conserved in the S46 DPP7/DPP11 family to Ala revealed that Phe664 of DPP7 and Phe671 of DPP11 primarily afforded hydrophobic P2 preference. A modeling study suggested that Phe664 and Gly666 of DPP7 and Phe671 and Arg673 of DPP11 being associated with the P2- and P1-position residues, respectively, are located adjacent to the catalytic Ser648/Ser655. The present results expand the substrate repertoire of DPP7, which ensures efficient degradation of oligopeptides in asaccharolytic bacteria.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phenylalanine 664 of dipeptidyl peptidase (DPP) 7 and Phenylalanine 671 of DPP11 mediate preference for P2‐position hydrophobic residues of a substrate

et al. 2013

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“…Dipeptidyl peptidase 3 (DPP3) is a metalloproteinase of the M49 family which contains a catalytic center with metal Zn 2+ as cofactor [ 17 , 18 ]. This family is characterized by the presence of two different motifs: HELLH and EEXR(K)AE(D), which are involved in the zinc coordination [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…This family is characterized by the presence of two different motifs: HELLH and EEXR(K)AE(D), which are involved in the zinc coordination [ 19 , 20 ]. In species such as human and yeast, it has been described that the main function of DPP3 is to hydrolyze peptides ranging from 3 to 10 amino acids in length from their N-terminal in dipeptides and free amino acids [ 17 , 18 , 20 ]. It has been also shown that DPP3 activity is inhibited by synthetic hermophin-like peptidases in rats and humans [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…The DPP3 is mainly located in the cytosol of distinct cell types such as those from human muscle, skin and neuroblastoma; also, it has been found in Drosophila melanogaster Schneider S2 cells, and Saccharomyces cerevisiae , amongst others [ 17 , 18 , 20 , 24 ]. In addition to its role in protein turnover, evidence suggests that DPP3 could be involved in more specific roles such as inhibition of the NF-E2–related factor 2 (NRF2) ubiquitination, which promotes the oxidative damage survival of cancer cells [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Dipeptidyl peptidase 3, a novel protease from Leishmania braziliensis

Díaz¹,

Ramírez²,

Nocua³

et al. 2018

PLoS ONE

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The increase of leishmaniasis cases worldwide and the emergence of Leishmania strains resistant to current treatments make necessary to find new therapeutic targets. Proteases are appealing drug targets because they play pivotal roles in facilitating parasite survival and promoting pathogenesis. Enzymes belonging to the dipeptidyl peptidase 3 (DPP3) group have been described in different organisms such as mammals, insects and yeast, in which these enzymes have been involved in both protein turnover and protection against oxidative damage. The aim of this work was to characterize the structure and function of the Leishmania braziliensis DPP3 (LbDPP3) protein as the first step to elucidate its suitability as a potential drug target. Sequence alignment showed 43% of identity between LbDPP3 and its human orthologous (hDPP3) enzyme. Although the modeled protein adopted a globally conserved three-dimensional (3D) structure, structural differences were found in the vicinity of the active site and the substrate binding-cleft. In addition, the Leishmania protein was expressed as a soluble recombinant protein and its kinetics parameters were determined using the z-Arginine-Arginine-AMC substrate. The LbDPP3 activity was maximal at pH values between 8.0–8.5. Interestingly, classical enzyme inhibitors such as the tynorphin and its derivative peptide IVYPW were found to actively inhibit the LbDPP3 activity. Moreover, these DPP3 inhibitors showed a detrimental effect upon parasite survival, decreasing the viability of promastigotes by up to 29%. Finally, it was observed that LbDPP3 was equally expressed along the in vitro differentiation from promastigotes to axenic amastigotes. In conclusion, these findings suggest that the L. brazileinsis DPP3 could be a promising drug target.

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Perspective of sodium reduction based on endogenous proteases via the strategy of sodium replacement in conjunction with mediated-curing

Zhang

Yin

et al. 2023

Critical Reviews in Food Science and Nutrition

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Dipeptidyl-Peptidase III

Cited by 5 publications

References 36 publications

Phenylalanine 664 of dipeptidyl peptidase (DPP) 7 and Phenylalanine 671 of DPP11 mediate preference for P2‐position hydrophobic residues of a substrate

Phenylalanine 664 of dipeptidyl peptidase (DPP) 7 and Phenylalanine 671 of DPP11 mediate preference for P2‐position hydrophobic residues of a substrate

Dipeptidyl peptidase 3, a novel protease from Leishmania braziliensis

Perspective of sodium reduction based on endogenous proteases via the strategy of sodium replacement in conjunction with mediated-curing

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