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https://doi.org/10.5562/cca1808

Human Dipeptidyl Peptidase III: the Role of Asn406 in Ligand Binding and Hydrolysis

Jasminka Špoljarić ; Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia
Antonija Tomić ; Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia
Bojana Vukelić ; Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia
Branka Salopek-Sondi ; Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia
Dejan Agić ; Department of Chemistry, Faculty of Agriculture, The Josip Juraj Strossmayer University, Trg Sv. Trojstva 3, 31107 Osijek, Croatia
Sanja Tomić ; Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia
Marija Abramić ; Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia

Puni tekst: engleski, pdf (5 MB) str. 259-268 preuzimanja: 661* citiraj
APA 6th Edition
Špoljarić, J., Tomić, A., Vukelić, B., Salopek-Sondi, B., Agić, D., Tomić, S. i Abramić, M. (2011). Human Dipeptidyl Peptidase III: the Role of Asn406 in Ligand Binding and Hydrolysis. Croatica Chemica Acta, 84 (2), 259-268. https://doi.org/10.5562/cca1808
MLA 8th Edition
Špoljarić, Jasminka, et al. "Human Dipeptidyl Peptidase III: the Role of Asn406 in Ligand Binding and Hydrolysis." Croatica Chemica Acta, vol. 84, br. 2, 2011, str. 259-268. https://doi.org/10.5562/cca1808. Citirano 22.07.2019.
Chicago 17th Edition
Špoljarić, Jasminka, Antonija Tomić, Bojana Vukelić, Branka Salopek-Sondi, Dejan Agić, Sanja Tomić i Marija Abramić. "Human Dipeptidyl Peptidase III: the Role of Asn406 in Ligand Binding and Hydrolysis." Croatica Chemica Acta 84, br. 2 (2011): 259-268. https://doi.org/10.5562/cca1808
Harvard
Špoljarić, J., et al. (2011). 'Human Dipeptidyl Peptidase III: the Role of Asn406 in Ligand Binding and Hydrolysis', Croatica Chemica Acta, 84(2), str. 259-268. https://doi.org/10.5562/cca1808
Vancouver
Špoljarić J, Tomić A, Vukelić B, Salopek-Sondi B, Agić D, Tomić S i sur. Human Dipeptidyl Peptidase III: the Role of Asn406 in Ligand Binding and Hydrolysis. Croatica Chemica Acta [Internet]. 2011 [pristupljeno 22.07.2019.];84(2):259-268. https://doi.org/10.5562/cca1808
IEEE
J. Špoljarić, et al., "Human Dipeptidyl Peptidase III: the Role of Asn406 in Ligand Binding and Hydrolysis", Croatica Chemica Acta, vol.84, br. 2, str. 259-268, 2011. [Online]. https://doi.org/10.5562/cca1808

Sažetak
Human dipeptidyl peptidase III (DPP III) is a member of the zinc-metallopeptidase family M49
with a role in intracellular protein catabolism. Ligand-free crystal structure of yeast and human orthologues
provided insight into the enzyme's active center and enabled some assumptions about the enzyme -
substrate interactions. The molecular modeling performed for human and yeast DPP III indicated involvement
of Asn406 and Asn415, respectively in ligand binding. To investigate further the role of this
asparagine residue, conserved in all eukaryotic M49 peptidases, a site-directed mutagenesis of human
DPP III was carried out. Replacement of Asn406 with Gln, but not with Ser, resulted in a large decrease in
the enzyme's binding affinity for competitive peptide inhibitor and in catalytic efficiency. Molecular dynamics
simulations performed for enzyme-substrate complexes, revealed changed coordination of the active-
site zinc ion and the orientation of the catalytically important His568, in N406Q, but not in the N406S
complexes.(doi: 10.5562/cca1808)

Ključne riječi
dipeptidyl peptidase III; molecular dynamics; peptidase family M49; protein structurefunction; site-directed mutagenesis

Hrčak ID: 71989

URI
https://hrcak.srce.hr/71989

Posjeta: 954 *