4WJL
Structure of human dipeptidyl peptidase 10 (DPPY): a modulator of neuronal Kv4 channels
Summary for 4WJL
| Entry DOI | 10.2210/pdb4wjl/pdb |
| Descriptor | 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) |
| Functional Keywords | inactive dipeptidyl peptidase 10, dpp4 structure homologue, alpha/beta hydrolase, beta-propeller, membrane protein |
| Biological source | Homo sapiens (Human) |
| Cellular location | Cell membrane ; Single-pass type II membrane protein : Q8N608 |
| Total number of polymer chains | 2 |
| Total formula weight | 168725.84 |
| Authors | Bezerra, G.A.,Dobrovetsky, E.,Seitova, A.,Fedosyuk, S.,Dhe-Paganon, S.,Gruber, K. (deposition date: 2014-09-30, release date: 2015-03-18, Last modification date: 2024-10-23) |
| Primary citation | 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 Cited by 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: 25740212DOI: 10.1038/srep08769 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.4 Å) |
Structure validation
Download full validation report
