{"title":"人类丝氨酸蛋白酶抑制剂(serpin)B9 的结晶和晶体学研究。","authors":"Teng Yan, Aiwu Zhou","doi":"10.1107/S2053230X24009439","DOIUrl":null,"url":null,"abstract":"<p>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 <i>P</i>2<sub>1</sub>2<sub>1</sub>2<sub>1</sub>, with unit-cell parameters <i>a</i> = 68.51, <i>b</i> = 82.32, <i>c</i> = 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.</p>","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":"80 11","pages":"286-293"},"PeriodicalIF":1.1000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Crystallization and crystallographic studies of human serine protease inhibitor (serpin) B9\",\"authors\":\"Teng Yan, Aiwu Zhou\",\"doi\":\"10.1107/S2053230X24009439\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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 <i>P</i>2<sub>1</sub>2<sub>1</sub>2<sub>1</sub>, with unit-cell parameters <i>a</i> = 68.51, <i>b</i> = 82.32, <i>c</i> = 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.</p>\",\"PeriodicalId\":7029,\"journal\":{\"name\":\"Acta crystallographica. Section F, Structural biology communications\",\"volume\":\"80 11\",\"pages\":\"286-293\"},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2024-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta crystallographica. Section F, Structural biology communications\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1107/S2053230X24009439\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta crystallographica. Section F, Structural biology communications","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1107/S2053230X24009439","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
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。
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.
期刊介绍:
Acta Crystallographica Section F is a rapid structural biology communications journal.
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