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通过溶液核磁共振对MALT1副胱天蛋白酶进行主链归属

Backbone Assignment of the MALT1 Paracaspase by Solution NMR.

作者信息

Unnerståle Sofia, Nowakowski Michal, Baraznenok Vera, Stenberg Gun, Lindberg Jimmy, Mayzel Maxim, Orekhov Vladislav, Agback Tatiana

机构信息

Medivir AB, PO Box 1086, SE-141 22, Huddinge, Sweden.

Swedish NMR Centre, University of Gothenburg, PO Box 465, SE-40530, Gothenburg, Sweden.

出版信息

PLoS One. 2016 Jan 20;11(1):e0146496. doi: 10.1371/journal.pone.0146496. eCollection 2016.

Abstract

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a unique paracaspase protein whose protease activity mediates oncogenic NF-κB signalling in activated B cell-like diffuse large B cell lymphomas (ABC-DLBCLs). ABC-DLBCLs are aggressive lymphomas with high resistance to current chemotherapies. Low survival rate among patients emphasizes the urgent need for alternative treatment options. The characterization of the MALT1 will be an essential tool for developing new target-directed drugs against MALT1 dependent disorders. As the first step in the atomic-level NMR studies of the system, here we report, the (15)N/(13)C/(1)H backbone assignment of the apo form of the MALT1 paracaspase region together with the third immunoglobulin-like (Ig3) domain, 44 kDa, by high resolution NMR. In addition, the non-uniform sampling (NUS) based targeted acquisition procedure is evaluated as a mean of decreasing acquisition and analysis time for larger proteins.

摘要

黏膜相关淋巴组织淋巴瘤易位蛋白1(MALT1)是一种独特的类半胱天冬酶蛋白,其蛋白酶活性在活化B细胞样弥漫性大B细胞淋巴瘤(ABC-DLBCL)中介导致癌性核因子κB信号传导。ABC-DLBCL是侵袭性淋巴瘤,对当前化疗具有高度抗性。患者生存率低凸显了迫切需要替代治疗方案。MALT1的特性将是开发针对MALT1依赖性疾病的新型靶向药物的重要工具。作为该系统原子水平核磁共振研究的第一步,我们在此报告通过高分辨率核磁共振对MALT1类半胱天冬酶区域的脱辅基形式与第三个免疫球蛋白样(Ig3)结构域(44 kDa)进行的(15)N/(13)C/(1)H主链归属。此外,基于非均匀采样(NUS)的靶向采集程序被评估为减少较大蛋白质采集和分析时间的一种方法。

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