کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2187809 | 1096140 | 2007 | 16 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Relationship between Propeptide pH Unfolding and Inhibitory Ability during ProDer p 1 Activation Mechanism Relationship between Propeptide pH Unfolding and Inhibitory Ability during ProDer p 1 Activation Mechanism](/preview/png/2187809.png)
The major allergen Der p 1 of the house dust mite Dermatophagoides pteronyssinus is a papain-like cysteine protease (CA1) produced as an inactive precursor and associated with allergic diseases. The propeptide of Der p 1 exhibits a specific fold that makes it unique in the CA1 propeptide family. In this study, we investigated the activation steps involved in the maturation of the recombinant protease Der p 1 expressed in Pichia pastoris and the interaction of the full-length and truncated soluble propeptides with their parent enzyme in terms of activity inhibition and BIAcore interaction analysis. According to our results, the activation of protease Der p 1 is a multistep mechanism that is characterized by at least two intermediates. The propeptide strongly inhibits unglycosylated and glycosylated recombinant Der p 1 (KD = 7 nM) at neutral pH. This inhibition is pH dependent. It decreases from pH 7 to pH 4 and can be related to conformational changes of the propeptide characterized by an increase of its flexibility and formation of a molten globule state. Our results indicate that activation of the zymogen at pH 4 is a compromise between activity preservation and propeptide unfolding.
Journal: Journal of Molecular Biology - Volume 374, Issue 1, 16 November 2007, Pages 170–185