4WJL

Structure of human dipeptidyl peptidase 10 (DPPY): a modulator of neuronal Kv4 channels

4WJL の概要

• エントリーDOI: 10.2210/pdb4wjl/pdb
• 分子名称: Inactive dipeptidyl peptidase 10, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: inactive dipeptidyl peptidase 10, dpp4 structure homologue, alpha/beta hydrolase, beta-propeller, membrane protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cell membrane ; Single-pass type II membrane protein : Q8N608
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 168725.84

構造登録者

Bezerra, G.A.,Dobrovetsky, E.,Seitova, A.,Fedosyuk, S.,Dhe-Paganon, S.,Gruber, K. (登録日: 2014-09-30, 公開日: 2015-03-18, 最終更新日: 2024-10-23)

主引用文献

Bezerra, G.A.,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, 5:8769-8769, 2015

PubMed Abstract: 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 β-propeller and a classical α/β-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.

PubMed: 25740212
DOI: 10.1038/srep08769

実験手法

X-RAY DIFFRACTION (3.4 Å)