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Expanded substrate specificity supported by P1′ and P2′ residues enables bacterial dipeptidyl-peptidase 7 to degrade bioactive peptides
http://hdl.handle.net/10069/00041312
http://hdl.handle.net/10069/000413128f063dff-bbc2-42b6-8941-17415cac169f
名前 / ファイル | ライセンス | アクション |
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JBC298_101585.pdf (1.1 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2022-03-14 | |||||
タイトル | ||||||
タイトル | Expanded substrate specificity supported by P1′ and P2′ residues enables bacterial dipeptidyl-peptidase 7 to degrade bioactive peptides | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | diabetes | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | dipeptidyl-peptidase | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | DPP4 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | DPP7 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | DPP11 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | incretin | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | insulin | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | mass spectrometry | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | periodontal disease | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | substrate specificity | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Ohara-Nemoto, Yuko
× Ohara-Nemoto, Yuko× Shimoyama, Yu× Ono, Toshio× Sarwar, Mohammad Tanvir× Nakasato, Manami× Sasaki, Minoru× Nemoto, Takayuki K. |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Dipeptide production from extracellular proteins is crucial for Porphyromonas gingivalis, a pathogen related to chronic periodontitis, because its energy production is entirely dependent on the metabolism of amino acids predominantly incorporated as dipeptides. These dipeptides are produced by periplasmic dipeptidyl-peptidase (DPP)4, DPP5, DPP7, and DPP11. Although the substrate specificities of these four DPPs cover most amino acids at the penultimate position from the N terminus (P1), no DPP is known to cleave penultimate Gly, Ser, Thr, or His. Here, we report an expanded substrate preference of bacterial DPP7 that covers those residues. MALDI-TOF mass spectrometry analysis demonstrated that DPP7 efficiently degraded incretins and other gastrointestinal peptides, which were successively cleaved at every second residue, including Ala, Gly, Ser, and Gln, as well as authentic hydrophobic residues. Intravenous injection of DPP7 into mice orally administered glucose caused declines in plasma glucagon-like peptide-1 and insulin, accompanied by increased blood glucose levels. A newly developed coupled enzyme reaction system that uses synthetic fluorogenic peptides revealed that the P1′ and P2′ residues of substrates significantly elevated kcat values, providing an expanded substrate preference. This activity enhancement was most effective toward the substrates with nonfavorable but nonrepulsive P1 residues in DPP7. Enhancement of kcat by prime-side residues was also observed in DPP11 but not DPP4 and DPP5. Based on this expanded substrate specificity, we demonstrate that a combination of DPPs enables proteolytic liberation of all types of N-terminal dipeptides and ensures P. gingivalis growth and pathogenicity. | |||||
書誌情報 |
Journal of Biological Chemistry 巻 298, 号 3, p. 101585, 発行日 2022-01-13 |
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出版者 | ||||||
出版者 | Elsevier Inc. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 00219258 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.jbc.2022.101585 | |||||
権利 | ||||||
権利情報 | © 2022 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Journal of Biological Chemistry, 298(3), art. no. 101585; 2022 |