STAFF PRIORITY TIME CRYSTAL STRUCTURE OF CYCLOPHILIN

工作人员优先时间亲环蛋白晶体结构

• 批准号: 6119369
• 负责人: PETER KUHN
• 金额: --
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6119369
• 关键词: biomaterials; proteins

Brugia Malayi is a mosquito-transmitted filarial nematode (roundworm) parasite of humans in South and South-East Asia from India in the west to Korea in the east. It is estimated that more than 100 million people worldwide are infected by filarial parasites and more than 1 billion live in areas where filariasis is common. Most of the symptoms associated with infection appear to arise from immune reactions rather than from the worms themselves. Immune responses to the worms, which reside in the lymphatic system, lead to lymphoedema. Bouts of fever and lymphangitis are common and, rarely, a chronic infection can also cause elephantitis. Cyclophilins (Cyp) are a family of proteins binding the immunosuppressive drug cyclosporin A (CsA), a neutral 11 amino acid cyclic peptide originally isolated from the fungus Tolypocladium inflatum. The Cyp/CsA complex supresses the immune system by inhibiting T-cell activation. Using crystals of CypBm grown at 4 C, we have demonstrated diffraction to a resolution of 1.05 E. We expect to collect data beyond this resolution in the near future. We have successfully grown crystals of CypBm complexed with CsA. Although the crystals are generally small (dimensions = 150 5m), intergrown and poorly-diffracting (limiting resolution around 3.0 E), data was successfully collected on a cryogenically frozen crystal at BL9-1 to a resolution of 2.5 E. The crystals belong to space group P21 with cell dimensions a=62 E, b=100 E, c=134 E, and _=94 . Completeness to 2.5 E was 97%, I/?(I) at 2.5 E was 1.6 and the overall multiplicity was 2.9. The structure, with 8 molecules of CycBm and 8 molecules of CsA in the asymmetric unit, was solved by molecular replacement using the known structure of CycBm. Refinement of the complex structure is in progress. The current crystallographic R-factor for a model including 8 CypBm molecules, 8 CsA molecules and solvent, is 24.6% for 53,370 reflections with d = 2.5 E.

马来丝虫是一种蚊媒丝虫 来自印度的南亚和东南亚人类的（蛔虫）寄生虫 从西边到东边的朝鲜 据估计，超过100 全世界有100万人感染了丝虫病， 超过10亿人生活在丝虫病常见的地区。 大部分 与感染相关的症状似乎是由免疫系统引起的， 而不是从蠕虫本身的反应。 免疫应答 寄生在淋巴系统中的蠕虫导致淋巴水肿。 发烧和淋巴管炎是常见的，很少，慢性 感染也会引起象皮炎。 亲环素（Cyp）是一种 结合免疫抑制药物环孢菌素A的蛋白质家族 (CsA)，一种中性的11个氨基酸的环肽，最初分离自 一种叫Tolypocladium inflatum的真菌。 Cyp/CsA复合物抑制 免疫系统通过抑制T细胞活化。 使用晶体 CypBm生长在4 ℃，我们已经证明了衍射的分辨率 1.05 E。我们希望收集的数据超过这一决议， 近期 我们已经成功地生长了CypBm复合晶体， 关于CsA 尽管晶体通常很小（尺寸= 150 5米），共生和衍射差（限制分辨率约3.0 E），在低温冷冻晶体上成功收集了数据 在BL 9 -1处，分辨率为2.5 E。晶体属于空间群 具有单元尺寸a=62 E，B=100 E，c=134 E，和_=94的P21。 对2.5E的完整性为97%，I/？(I)在2.5 E时为1.6， 多重性为2.9。 结构，具有8个CycBm分子和8个 分子的CsA在不对称单元，解决了分子 使用CycBm的已知结构进行置换。 细化 复杂的结构正在进行中。 当前的晶体学 包括8个CypBm分子、8个CsA分子和8个CsA分子的模型的R因子 对于d = 2.5 E的53，370次反射，溶剂的回收率为24.6%。