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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
http://hdl.handle.net/10069/31580
http://hdl.handle.net/10069/3158008cbeddd-6323-47cd-bf10-22099ed53e2a
名前 / ファイル | ライセンス | アクション |
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FEBSOB3_177.pdf (1.2 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2013-05-01 | |||||
タイトル | ||||||
タイトル | Phenylalanine 664 of dipeptidyl peptidase (DPP) 7 and Phenylalanine 671 of DPP11 mediate preference for P2-position hydrophobic residues of a substrate | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Dipeptidyl-peptidase | |||||
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 | P2 position | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Porphyromonas gingivalis | |||||
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 |
Rouf, Shakh M.A.
× Rouf, Shakh M.A.× Ohara-Nemoto, Yuko× Ono, Toshio× Shimoyama, Yu× Kimura, Shigenobu× Nemoto, Takayuki K. |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. | |||||
書誌情報 |
FEBS Open Bio 巻 3, p. 177-183, 発行日 2013 |
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出版者 | ||||||
出版者 | Elsevier B.V. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 22115463 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.fob.2013.03.004 | |||||
権利 | ||||||
権利情報 | © 2013 The Authors. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies. | |||||
権利 | ||||||
権利情報 | This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |||||
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 | FEBS Open Bio, 3, pp.177-183; 2013 |