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Goliyon Ki Raasleela Ram-leela In Hindi 720p.zip
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. bollywood movies in hindi mp4. above average info about information about bollywood movies in hindi mp4. 90 min full album zip. -kothnani2018 flv.ADAMTS13: Mass spectrometry reveals novel cleavage sites and heterogeneity in different Japanese individuals.
ADAMTS13 is a von Willebrand factor-cleaving protease and a key enzyme in the control of thrombosis. Mutations in the ADAMTS13 gene are the cause of thrombotic thrombocytopenic purpura and Bernard-Soulier syndrome. However, all disease-associated variants identified to date have been detected by conventional sequencing, revealing that ADAMTS13 is a structurally complex molecule with more than 100 potential cleavage sites. We recently reported that a metallo-endopeptidase could cleave ADAMTS13 at a new site, T737-W740. To gain further insight into the structure and molecular mechanism of ADAMTS13, we characterized the enzymatic mechanism of ADAMTS13 by using mass spectrometry-based proteomics. After screening a panel of 19 commercially available recombinant proteins, including those synthesized as C-terminal hexa-his-tagged proteins, we identified thrombomodulin as a candidate enzyme. We then examined the structural and enzymatic properties of ADAMTS13 synthesized using the HEK293 cell-line. Digestion of ADAMTS13 by thrombomodulin resulted in release of full-length ADAMTS13 as well as a core fragment comprising the metalloprotease domain and its propeptide. The identified cleavage site was confirmed by LC-MS/MS. In addition, we found that ADAMTS13 is highly heterogeneous. Using mass spectrometry, we identified 8 catalytic sites and 26 potential intra- and interchain disulfide bonds. Taken together, this study identifies novel cleavage sites, structural heterogeneity and possible linkage sites in ADAMTS13, which should be considered for the development of ADAMTS13-targeting therapies.
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