کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10757979 | 1050401 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
S1 pocket of glutamate carboxypeptidase II: A new binding site for amyloid-β degradation
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
We recently reported that glutamate carboxypeptidase II (GCPII) has a new physiological function degrading amyloid-β (Aβ), distinct from its own hydrolysis activity in N-acetyl-L-aspartyl-L-glutamate (NAAG); however, its underlying mechanism remains undiscovered. Using site-directed mutagenesis and S1 pocket-specific chemical inhibitor (compound 2), which was developed for the present study based on in sillico computational modeling, we discovered that the Aβ degradation occurs through S1 pocket but not through S1Ⲡpocket responsible for NAAG hydrolysis. Treatment with compound 2 prevented GCPII from Aβ degradation without any impairment in NAAG hydrolysis. Likewise, 2-PMPA (specific GCPII inhibitor developed targeting S1Ⲡpocket) completely blocked the NAAG hydrolysis without any effect on Aβ degradation. Pre-incubation with NAAG and Aβ did not affect Aβ degradation and NAAG hydrolysis, respectively. These data suggest that GCPII has two distinctive binding sites for two different substrates and that Aβ degradation occurs through binding to S1 pocket of GCPII.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 438, Issue 4, 6 September 2013, Pages 765-771
Journal: Biochemical and Biophysical Research Communications - Volume 438, Issue 4, 6 September 2013, Pages 765-771
نویسندگان
Suk Kyung Lee, Hyunyoung Kim, You-Hoon Cheong, Min-Ju Kim, Sangmee Ahn Jo, Hyung-Seop Youn, Sang Ick Park,