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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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Volume 396, Issue 4

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Aspartate 496 from the subsite S2 drives specificity of human dipeptidyl peptidase III

Marija Abramić
  • Corresponding author
  • Division of Organic Chemistry and Biochemistry, Ruder Bošković Institute, Bijenička cesta 54, P.O. Box 180, HR-10002 Zagreb, Croatia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Zrinka Karačić
  • Division of Organic Chemistry and Biochemistry, Ruder Bošković Institute, Bijenička cesta 54, P.O. Box 180, HR-10002 Zagreb, Croatia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Maja Šemanjski
  • Division of Organic Chemistry and Biochemistry, Ruder Bošković Institute, Bijenička cesta 54, P.O. Box 180, HR-10002 Zagreb, Croatia
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  • De Gruyter OnlineGoogle Scholar
/ Bojana Vukelić
  • Division of Organic Chemistry and Biochemistry, Ruder Bošković Institute, Bijenička cesta 54, P.O. Box 180, HR-10002 Zagreb, Croatia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Nina Jajčanin-Jozić
  • Division of Organic Chemistry and Biochemistry, Ruder Bošković Institute, Bijenička cesta 54, P.O. Box 180, HR-10002 Zagreb, Croatia
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  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-01-10 | DOI: https://doi.org/10.1515/hsz-2014-0247

Abstract

Human dipeptidyl peptidase III (hDPP III) is a member of the M49 metallopeptidase family, which is involved in intracellular protein catabolism and oxidative stress response. To investigate the structural basis of hDPP III preference for diarginyl arylamide, using site-directed mutagenesis, we altered its S2 subsite to mimic the counterpart in yeast enzyme. Kinetic studies revealed that the single mutant D496G lost selectivity due to the increase of the Km value. The D496G, but not S504G, showed significantly decreased binding of peptides with N-terminal arginine, and of tynorphin. The results obtained identify Asp496 as an important determinant of human DPP III substrate specificity.

This article offers supplementary material which is provided at the end of the article.

Keywords: metallopeptidase; site-directed mutagenesis; substrate specificity; zinc enzyme

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About the article

Corresponding author: Marija Abramić, Division of Organic Chemistry and Biochemistry, Ruder Bošković Institute, Bijenička cesta 54, P.O. Box 180, HR-10002 Zagreb, Croatia, e-mail:


Received: 2014-09-09

Accepted: 2015-01-02

Published Online: 2015-01-10

Published in Print: 2015-04-01


Citation Information: Biological Chemistry, Volume 396, Issue 4, Pages 359–366, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2014-0247.

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