Structural highlights
Disease
DPP10_HUMAN Disease susceptibility is associated with variations affecting the gene represented in this entry.
Function
DPP10_HUMAN Promotes cell surface expression of the potassium channel KCND2 (PubMed:15454437). Modulates the activity and gating characteristics of the potassium channel KCND2 (PubMed:15454437). Has no dipeptidyl aminopeptidase activity (PubMed:12662155).[1] [2] [3]
Publication Abstract from PubMed
The voltage-gated potassium channel family (Kv) constitutes the most diverse class of ion channels in the nervous system. Dipeptidyl peptidase 10 (DPP10) is an inactive peptidase that modulates the electrophysiological properties, cell-surface expression and subcellular localization of voltage-gated potassium channels. As a consequence, DPP10 malfunctioning is associated with neurodegenerative conditions like Alzheimer and fronto-temporal dementia, making this protein an attractive drug target. In this work, we report the crystal structure of DPP10 and compare it to that of DPP6 and DPP4. DPP10 belongs to the S9B serine protease subfamily and contains two domains with two distinct folds: a beta-propeller and a classical alpha/beta-hydrolase fold. The catalytic serine, however, is replaced by a glycine, rendering the protein enzymatically inactive. Difference in the entrance channels to the active sites between DPP10 and DPP4 provide an additional rationale for the lack of activity. We also characterize the DPP10 dimer interface focusing on the alternative approach for designing drugs able to target protein-protein interactions.
Structure of human dipeptidyl peptidase 10 (DPPY): a modulator of neuronal Kv4 channels.,Bezerra GA, Dobrovetsky E, Seitova A, Fedosyuk S, Dhe-Paganon S, Gruber K Sci Rep. 2015 Mar 5;5:8769. doi: 10.1038/srep08769. PMID:25740212[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Qi SY, Riviere PJ, Trojnar J, Junien JL, Akinsanya KO. Cloning and characterization of dipeptidyl peptidase 10, a new member of an emerging subgroup of serine proteases. Biochem J. 2003 Jul 1;373(Pt 1):179-89. PMID:12662155 doi:http://dx.doi.org/10.1042/BJ20021914
- ↑ Jerng HH, Qian Y, Pfaffinger PJ. Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase 10 (DPP10). Biophys J. 2004 Oct;87(4):2380-96. PMID:15454437 doi:http://dx.doi.org/10.1529/biophysj.104.042358
- ↑ Zagha E, Ozaita A, Chang SY, Nadal MS, Lin U, Saganich MJ, McCormack T, Akinsanya KO, Qi SY, Rudy B. DPP10 modulates Kv4-mediated A-type potassium channels. J Biol Chem. 2005 May 13;280(19):18853-61. Epub 2005 Jan 25. PMID:15671030 doi:http://dx.doi.org/M410613200
- ↑ Bezerra GA, Dobrovetsky E, Seitova A, Fedosyuk S, Dhe-Paganon S, Gruber K. Structure of human dipeptidyl peptidase 10 (DPPY): a modulator of neuronal Kv4 channels. Sci Rep. 2015 Mar 5;5:8769. doi: 10.1038/srep08769. PMID:25740212 doi:http://dx.doi.org/10.1038/srep08769
