Jump to main content
Jump to site search

Issue 58, 2017, Issue in Progress
Previous Article Next Article

New findings about human dipeptidyl peptidase III based on mutations found in cancer

Author affiliations

Abstract

Dipeptidyl peptidase III (DPP III) is a cytosolic enzyme belonging to the metallopeptidase family M49, involved in the final steps of protein catabolism. More than a hundred missense mutations can be found in the coding region of the human DPP3 gene when searching cBioPortal for Cancer Genomics. The role of two highly conserved residues in the family M49, whose mutations G313W and R510W were detected in human cancer, was investigated using combined experimental and computational approaches (substrate docking and MD simulations). Several mutants of human DPP III were expressed and purified as recombinant proteins, and their biochemical properties were determined. The conservative substitution of Arg510 with lysine mildly decreased enzyme activity activity for Arg-Arg-2-naphtylamide substrate, while the substitutions of Arg510 with glutamine and Gly313 with alanine substantially decreased enzyme activity, and tryptophan substitutions found in cancer, G313W and R510W, almost abolished enzyme activity. MD simulations showed that substitution of Gly313, and especially Arg510 with tryptophan, significantly increases the enzyme flexibility, particularly that of the binding site including the H450ELLGH455 motif, and influences the substrate interactions with the catalytic His568. The results clearly indicate that, besides the enzyme structure, its dynamics properties also significantly influence the human DPP III activity.

Graphical abstract: New findings about human dipeptidyl peptidase III based on mutations found in cancer

Back to tab navigation

Supplementary files

Article information


Submitted
03 Mar 2017
Accepted
13 Jul 2017
First published
21 Jul 2017

This article is Open Access

RSC Adv., 2017,7, 36326-36334
Article type
Paper

New findings about human dipeptidyl peptidase III based on mutations found in cancer

M. Matovina, D. Agić, M. Abramić, S. Matić, Z. Karačić and S. Tomić, RSC Adv., 2017, 7, 36326
DOI: 10.1039/C7RA02642K

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements