CRYSTAL STRUCTURE OF MTCP 1, AN ONCOGENE EXPRESSED IN T CELL MALIGNANCIES

T 细胞恶性肿瘤中表达的癌基因 MTCP 1 的晶体结构

• 批准号: 6120542
• 负责人: Irene T Weber
• 金额: $ 0.02万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 1999-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6120542
• 关键词: bioimaging /biomedical imaging; biological products; biomedical resource; proteins; radiography; structural biology

Mature T-cell Proliferation Factor 1 (MTCP-1) and TCL-1 genes form a novel family that is involved in T-cell malignancies and lymphoid proliferation. TCL-1 and MTCP-1 oncogenes encode for 14kDa proteins that share 41% identical amino acid residues but have no significant similarities with other known proteins. The crystal structure of MTCP-1 will be used to design mutations to study the function, and peptide analogs as potential drugs for treatment of T-cell malignancies. Crystals of MTCP-1 grow in space group P6 with the unit cell dimensions of a = b = 61.41 and c = 87.31
. The crystals diffract to 2.5-2.0
resolution, three potential heavy atom derivatives have been found, and phases result in a partially interpretable electron density map. There are two problems: the X-ray data are weak and radiation decay reduces the accuracy of the measurements; and the derivatives are not mutually isomorphous. Synchrotron time is requested to obtain accurate high resolution data for the native and anomalous data for the derivatives in order to improve the phases. We are also preparing selenomethionine enriched MTCP-1 for MAD phasing.

成熟 T 细胞增殖因子 1 (MTCP-1) 和 TCL-1 基因形成 一个涉及 T 细胞恶性肿瘤和淋巴系统的新家族 增殖。 TCL-1 和 MTCP-1 癌基因编码 14kDa 蛋白质 共享 41% 相同的氨基酸残基，但没有显着性 与其他已知蛋白质的相似性。 晶体结构 MTCP-1将用于设计突变来研究功能，并且 肽类似物作为治疗 T 细胞的潜在药物 恶性肿瘤。 MTCP-1 晶体在 P6 空间群中生长 a = b = 61.41 和 c = 87.31 的单元尺寸。 晶体 衍射至 2.5-2.0 分辨率，三个潜在重原子 已经发现了衍生物，并且阶段导致了部分 可解释的电子密度图。 有两个问题： X 射线数据较弱，辐射衰减降低了测量的准确性 测量；并且导数不是互同构的。 要求同步加速器时间以获得准确的高分辨率数据 对于衍生品的本机数据和异常数据，以便 改进阶段。 我们还准备了富含硒代蛋氨酸的 MTCP-1 用于 MAD 定相。