کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5131899 1378781 2017 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
SerpinI2 (pancpin) is an inhibitory serpin targeting pancreatic elastase and chymotrypsin
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
SerpinI2 (pancpin) is an inhibitory serpin targeting pancreatic elastase and chymotrypsin
چکیده انگلیسی


- SerpinI2 cloning and recombinant protein production
- SerpinI2 is an inhibitory serpin that displays native instability.
- SerpinI2 targets pancreatic chymotrypsin and elastase.
- SerpinI2 can readily polymerise.

SerpinI2/Pancpin/MEPI is a 46 kDa member of the serpin (serine protease inhibitor) superfamily. It is downregulated in pancreatic and breast cancer, and associated with acinar cell apoptosis and pancreatic insufficiency when absent in mice. However, the target protease and protein properties of serpinI2 are previously uncharacterised. We have expressed and purified recombinant serpin I2 in E. coli. The protein exhibited thermal instability typical of inhibitory serpins, which was lost following RCL cleavage. SerpinI2 did not inhibit trypsin, but was found to inhibit pancreatic chymotrypsin and elastase with Kass values > 105 M− 1 s− 1, and with stoichiometry of inhibition of 1.4 and 1.7 respectively. Mutagenesis of the predicted critical hinge region residue Ser344 abolished inhibitory activity, and a cleavage site C-terminal to Met358 was identified. The protein is also prone to polymerisation/aggregation at 45 °C, a characteristic of serpins associated with disease. This study therefore reveals a function for serpinI2 and supports the hypothesis that this protein can protect pancreatic cells from prematurely activated zymogens.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics - Volume 1865, Issue 2, February 2017, Pages 195-200
نویسندگان
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