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Structure of human dipeptidyl peptidase 10 (DPPY): a modulator of neuronal Kv4 channels
Structural highlights
DiseaseDPP10_HUMAN Disease susceptibility is associated with variations affecting the gene represented in this entry. FunctionDPP10_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 PubMedThe 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 AlsoReferences
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