Structural Substrate Conditions Required for Neutral Endopeptidase-Mediated Natriuretic Peptide Degradation |
| |
Authors: | Kristin Pankow Anja Schwiebs Matthias Becker Gerd Krause |
| |
Institution: | 1 Fachbereich Biologie, Chemie, Pharmazie, Freie Universität Berlin, Königin-Luise-Str. 2+4, D-14195 Berlin, Germany 2 Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Str. 10, D-13125 Berlin, Germany 3 Centre for Biomedical Research, Hull York Medical School, University of Hull, Hull, UK 4 Excellence Cluster Cardio-Pulmonary System, Justus-Liebig-Universität Giessen, Aulweg 130, D-35392 Giessen, Germany |
| |
Abstract: | Natriuretic peptides are cyclic vasoactive peptide hormones with great diagnostic and therapeutic relevance. The main catabolic pathway postulated for natriuretic peptides is the degradation by neutral endopeptidase (NEP). However, B-type natriuretic peptide has been found to be resistant to NEP. Here, we compared the degradation of various mature, truncated, and recombinant natriuretic peptides by NEP. The degradation was clearly dependent on the length of the N- or C-terminus as well as on distinct sequence differences within the essential loop structure of the natriuretic peptides. Based on these findings, we developed a model for the interaction of NEP and natriuretic peptides that enables new insights into the mode of action and prediction of substrates of NEP, a peptidase that plays a key role in crucial (patho-) physiological processes. |
| |
Keywords: | ANP atrial natriuretic peptide BNP B-type natriuretic peptide CNP C-type natriuretic peptide DNP Dendroaspis natriuretic peptide NEP neutral endopeptidase hANP human ANP mNEP murine NEP hBNP human BNP 3D three-dimensional mANP mouse ANP mBNP mouse BNP pBNP porcine BNP chim chimeric eANP eel ANP chANP chicken ANP PDB Protein Data Bank |
本文献已被 ScienceDirect 等数据库收录! |
|