Pankow Kristin, Schwiebs Anja, Becker Matthias, Siems Wolf-Eberhard, Krause Gerd, Walther Thomas
Fachbereich Biologie, Freie Universität Berlin, Germany.
J Mol Biol. 2009 Oct 23;393(2):496-503. doi: 10.1016/j.jmb.2009.08.025. Epub 2009 Aug 15.
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.
利钠肽是一类具有重要诊断和治疗意义的环状血管活性肽激素。推测利钠肽的主要分解代谢途径是由中性内肽酶（NEP）进行降解。然而，已发现B型利钠肽对NEP具有抗性。在此，我们比较了NEP对各种成熟、截短和重组利钠肽的降解情况。降解明显取决于N端或C端的长度以及利钠肽关键环结构内不同的序列差异。基于这些发现，我们建立了一个NEP与利钠肽相互作用的模型，该模型有助于深入了解NEP的作用模式并预测其底物，NEP是一种在关键（病理）生理过程中起关键作用的肽酶。
