The precise biological function of human dipeptidyl peptidase III (hDPP III) is poorly understood. Using luciferase reporter constructs responsive to change in Ca2+ and/or cAMP and Fura 2-AM fluorometric assay, we show a significant decrease in intracellular Ca2+ following hDPP III overexpression and angiotensin II stimulation in angiotensin II type 1 receptor (G-protein coupled receptor, GPCR) expressing HEK293T cells. Silencing the expression of hDPP III by siRNA reversed the effect of hDPP III overexpression with a concomitant increase in Ca2+. These results, for the first time, show involvement of hDPP III in GPCR dependent Ca2+ regulation in HEK293T cells.
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http://dx.doi.org/10.1515/hsz-2016-0117 | DOI Listing |
J Biomol Struct Dyn
September 2022
Faculty of Food Technology Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
Dipeptidyl peptidase III (DPP III) is a zinc-dependent enzyme that sequentially hydrolyzes biologically active peptides by cleaving dipeptides from their N-termini. Although its fundamental role is not been fully elucidated, human DPP III (hDPP III) has been recognized in several pathophysiological processes of interest for drug development. In this article 27 quinazolinone-Schiff's bases were studied for their inhibitory activity against hDPP III combining an in vitro experiment with a computational approach.
View Article and Find Full Text PDFMolecules
October 2021
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China.
Human dipeptidyl-peptidase III (hDPP III) is capable of specifically cleaving dipeptides from the N-terminal of small peptides with biological activity such as angiotensin II (Ang II, DRVYIHPF), and participates in blood pressure regulation, pain modulation, and the development of cancers in human biological activities. In this study, 500 ns molecular dynamics simulations were performed on free-hDPP III (PDB code: 5E33), hDPP III-Ang II (PDB code: 5E2Q), and hDPP III-IVYPW (PDB code: 5E3C) to explore how these two peptides affect the catalytic efficiency of enzymes in terms of the binding mode and the conformational changes. Our results indicate that in the case of the hDPP III-Ang II complex, subsite S1 became small and hydrophobic, which might be propitious for the nucleophile to attack the substrate.
View Article and Find Full Text PDFMolecules
August 2021
Division of Organic Chemistry & Biochemistry, Ruđer Bošković Institute, P.O. Box 180, HR-10002 Zagreb, Croatia.
Novel dyes were prepared by simple "click CuAAC" attachment of a triarylborane-alkyne to the azide side chain of an amino acid yielding triarylborane dye which was conjugated with pyrene (dye ) forming a triarylborane-pyrene FRET pair. In contrast to previous cationic triarylboranes, the novel neutral dyes interact only with proteins, while their affinity to DNA/RNA is completely abolished. Both the reference triarylborane amino acid and triarylborane-pyrene conjugate bind to BSA and the hDPP III enzyme with high affinities, exhibiting a strong (up to 100-fold) fluorescence increase, whereby the triarylborane-pyrene conjugate additionally retained FRET upon binding to the protein.
View Article and Find Full Text PDFPharmaceuticals (Basel)
June 2021
Faculty of Agrobiotechnical Sciences Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
Dipeptidyl peptidase III (DPP III), a zinc-dependent exopeptidase, is a member of the metalloproteinase family M49 with distribution detected in almost all forms of life. Although the physiological role of human DPP III (hDPP III) is not yet fully elucidated, its involvement in pathophysiological processes such as mammalian pain modulation, blood pressure regulation, and cancer processes, underscores the need to find new hDPP III inhibitors. In this research, five series of structurally different coumarin derivatives were studied to provide a relationship between their inhibitory profile toward hDPP III combining an in vitro assay with an in silico molecular modeling study.
View Article and Find Full Text PDFPhys Chem Chem Phys
June 2021
Ruđer Bošković Institute, Division of Organic Chemistry and Biochemistry, Croatia.
Dipeptidyl peptidase III (DPP III), a zinc-dependent exopeptidase, is widely distributed in organisms and present in almost all human tissues. In addition to its involvement in protein catabolism, it plays a role in oxidative stress and blood pressure regulation, and there is evidence of its involvement in pain modulation. Excess zinc ions have been found to inhibit its hydrolytic activity, but the binding affinity, binding site geometry, and mechanism of inhibitory activity have been unknown.
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