解决人类pp60c-src SH2结构域与磷酸化酪氨酸五肽。
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徐RX,文字JM,戴维斯DG,溜冰场MJ,威拉德DH Jr Gampe RT Jr
解决人类pp60c-src SH2结构域与磷酸化酪氨酸五肽。
生物化学。1995年2月21日,34(7):2107 - 21所示。
- PubMed ID
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7532003 (在PubMed]
- 文摘
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人类pp60c-src细胞nonreceptor酪氨酸激酶,参与胞质信号转导和与恶性肿瘤的发展在人类乳腺癌和结肠癌。信号转导是由高度特定的SH2域之间的相互作用和受体磷酸化酪氨酸绑定图案。阐明分子构象和交互的解决方案,一个家庭的高度解决核磁共振(NMR)决心为src SH2结构域与高亲和性磷酸化五肽混合时,acetyl-p YEEIE-OH。23结构,生成距离几何(DG)和动态模拟退火(SA)过程,满足2072实验限制来源于各种各样的多频/多维和isotope-filtered NMR数据。叠加的残留143 - 245的平均坐标设置了一个原子rmsd 0.58 + / - 0.09 N,α,C原子和1.04 + / - 0.08的所有non-hydrogen原子。残留在命令二级结构区域重叠0.29 + / - 0.04 N,α,C”和0.73 + / - 0.08的所有non-hydrogen原子。角φ有序参数计算,ψ角> 0.9 81 106蛋白质残留。蛋白质构象特征主要有三个反平行的beta-strands,遍历一个紧凑的核心与一个阿尔法螺旋两侧附近的核心N - c终端。观察到分子间核奥佛好塞效应(一)pY, e + 1, + 3我残留定位配体在一个扩展的构象SH2域表面与pY和+ 3我侧链插入蛋白质绑定的口袋。一般来说,蛋白质的构象与之前报道不同的SH2结构域一致复合体由x射线晶体学。 However, inter- or intramolecular interactions involving the guanidinium side chains of the solvated R alpha A2 or the buried R beta B5 were not observed at pH = 5.5 or 7.0. If such interactions exist in solution, the absence of any confirming data probably arises from rapid exchange with solvent and/or undetermined dynamic components. Thus, the unrestrained R alpha A2 side chain did not show an amino-aromatic interaction or a hydrogen bond to the -1 carbonyl oxygen as observed in the crystal structures. This result is consistent with the solution structure of a different SH2 domain complex. A more detailed comparison between the crystal structure and the NMR-derived solution structures of the same src SH2 domain complex is presented.(ABSTRACT TRUNCATED AT 400 WORDS)