人类丝氨酸蛋白酶抑制剂(serpin)B9 的结晶和晶体学研究。

IF 1.1 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS
Teng Yan, Aiwu Zhou
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引用次数: 0

摘要

丝氨酸蛋白酶抑制剂 B9(serpin B9,又称蛋白酶抑制剂 9 或 PI9)通过特异性抑制细胞毒性 T 淋巴细胞和自然杀伤细胞中的丝氨酸蛋白酶颗粒酶 B,在调节免疫反应方面发挥着关键作用。尽管血清素 B9 有可能成为抗癌药物的靶点,但其结构细节至今仍难以捉摸。本研究成功制备了重组人血清素 B9 的裂解形式并将其结晶化。晶体属于空间群 P212121,单位晶胞参数为 a = 68.51、b = 82.32、c = 101.17 Å,并采集到分辨率为 1.9 Å 的 X 射线衍射数据集。该结构表明,丝蛋白酶 B9 采用了松弛构象,其裂解的反应中心环插入了中心 β 片层。与其他血清素不同的是,血清素 B9 在螺旋 D 周围显示出明显的结构偏差,具有较大的表面空腔,可作为小分子抑制剂的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Crystallization and crystallographic studies of human serine protease inhibitor (serpin) B9

Crystallization and crystallographic studies of human serine protease inhibitor (serpin) B9

Serine protease inhibitor B9 (serpin B9, also known as protease inhibitor 9 or PI9) plays a critical role in regulating the immune response by specifically inhibiting granzyme B, a serine protease found in cytotoxic T lymphocytes and natural killer cells. Despite its potential as an anticancer drug target, the structural details of serpin B9 have remained elusive until now. In this study, a cleaved form of recombinant human serpin B9 was successfully prepared and crystallized. The crystals belonged to space group P212121, with unit-cell parameters a = 68.51, b = 82.32, c = 101.17 Å, and an X-ray diffraction data set was collected at 1.9 Å resolution. The structure shows that serpin B9 adopts a relaxed conformation, with its cleaved reactive-centre loop inserted into the central β-sheet. Unlike other serpins, serpin B9 shows significant structural deviations around helix D, with a larger surface cavity, which could serve as a promising target for small-molecule inhibitors.

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来源期刊
Acta crystallographica. Section F, Structural biology communications
Acta crystallographica. Section F, Structural biology communications BIOCHEMICAL RESEARCH METHODSBIOCHEMISTRY &-BIOCHEMISTRY & MOLECULAR BIOLOGY
CiteScore
1.90
自引率
0.00%
发文量
95
期刊介绍: Acta Crystallographica Section F is a rapid structural biology communications journal. Articles on any aspect of structural biology, including structures determined using high-throughput methods or from iterative studies such as those used in the pharmaceutical industry, are welcomed by the journal. The journal offers the option of open access, and all communications benefit from unlimited free use of colour illustrations and no page charges. Authors are encouraged to submit multimedia content for publication with their articles. Acta Cryst. F has a dedicated online tool called publBio that is designed to make the preparation and submission of articles easier for authors.
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