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首页> 外文期刊>Acta crystallographica. Section D, Structural biology. >Coping with strong translational noncrystallographic symmetry and extreme anisotropy in molecular replacement with Phaser Phaser : human Rab27a
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Coping with strong translational noncrystallographic symmetry and extreme anisotropy in molecular replacement with Phaser Phaser : human Rab27a

机译：应对强大的转化noncrystallographic对称和极端各向异性分子与移相器更换移相器:人类Rab27a

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摘要

Data pathologies caused by effects such as diffraction anisotropy and translational noncrystallographic symmetry (tNCS) can dramatically complicate the solution of the crystal structures of macromolecules. Such problems were encountered in determining the structure of a mutant form of Rab27a, a member of the Rab GTPases. Mutant Rab27a constructs that crystallize in the free form were designed for use in the discovery of drugs to reduce primary tumour invasiveness and metastasis. One construct, hRab27a Mut , crystallized within 24?h and diffracted to 2.82?? resolution, with a unit cell possessing room for a large number of protein copies. Initial efforts to solve the structure using molecular replacement by Phaser were not successful. Analysis of the data set revealed that the crystals suffered from both extreme anisotropy and strong tNCS. As a result, large numbers of reflections had estimated standard deviations that were much larger than their measured intensities and their expected intensities, revealing problems with the use of such data at the time in Phaser . By eliminating extremely weak reflections with the largest combined effects of anisotropy and tNCS, these problems could be avoided, allowing a molecular‐replacement solution to be found. The lessons that were learned in solving this structure have guided improvements in the numerical analysis used in Phaser , particularly in identifying diffraction measurements that convey very little information content. The calculation of information content could also be applied as an alternative to ellipsoidal truncation. The post‐mortem analysis also revealed an oversight in accounting for measurement errors in the fast rotation function. While the crystal of mutant Rab27a is not amenable to drug screening, the structure can guide new modifications to obtain more suitable crystal forms.
机译：数据病理等造成的影响衍射各向异性和转化noncrystallographic对称(跨国公司)显著的解决复杂化晶体结构的大分子。问题是遇到了在决定Rab27a的变异形式,结构的成员Rab gtpase。结晶的自由形式的设计使用药物来减少主要的发现肿瘤的侵袭性和转移。构造,hRab27a傻瓜,固定在24 ?和衍射2.82 ? ?细胞拥有大量的空间蛋白质副本。使用分子结构由移相器更换没有成功。表明晶体患有两种极端的各向异性和强大的跨国公司。大量的反射估计远远大于标准差测量强度和预期使用强度,揭示问题这些数据在移相器。极度疲弱与最大的反射结合各向异性的影响以及跨国公司,这些问题可以避免,允许分子检测替代解决方案。在解决这一教训结构有指导改善数值分析中使用的移相器,特别是在确定衍射测量传达信息内容很少。也可以计算的信息内容应用作为一个椭圆形的替代品截断。揭示了会计的监督测量误差的快速旋转的功能。而变异的水晶Rab27a不是服从药物筛选、结构指导新修改获得更合适晶体形态。

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