Continuous and discontinuous changes in the unit cell of HIV-1 reverse transcriptase crystals on dehydration
Continuous and discontinuous changes in the unit cell of HIV-1 reverse transcriptase crystals on dehydration
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DOI：
10.1107/s0907444998004284
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发表时间：
1998-09-01
影响因子：
2.2
通讯作者：
Stuart, DI
中科院分区：
文献类型：
--
作者：
Esnouf, RM;Ren, JS;Stuart, DI
与抑制剂复合的HIV-1逆转录酶（RT）的晶体形式显示出3.7埃的高分辨率极限衍射。在浸泡实验中观察到这些晶体的晶胞尺寸的不稳定性，但这种变化的范围和随之而来的晶格顺序的变化揭示了一个机会观察脱水。有意诱导的脱水导致晶体具有各种晶胞，其中最好的有序显示衍射到2.2埃的最小布拉格间距。为了了解这种现象的分子基础，脱水的初步观察，脱水晶体的数据集，晶体包装和RT的域构象进行了详细分析。这种分析表明，晶体经历了显着的变化后，各种可能的脱水途径：一些变化逐渐发生，而另一些是突然的，需要显着的域重排。比较不同晶体形式中的畴排列，可以深入了解RT的灵活性，依次可能反映了允许这种治疗上重要的酶实现其生物功能的内部运动。
A crystal form of HIV-1 reverse transcriptase (RT) complexed with inhibitors showed diffraction to a high-resolution limit of 3.7 Angstrom. Instability in the unit-cell dimensions of these crystals was observed during soaking experiments, but the range of this variability and consequent change in lattice order was revealed by a chance observation of dehydration. Deliberately induced dehydration results in crystals having a variety of unit cells, the best-ordered of which show diffraction to a minimum Bragg spacing of 2.2 Angstrom. In order to understand the molecular basis for this phenomenon, the initial observation of dehydration, the data sets from dehydrated crystals, the crystal packing and the domain conformation of RT are analysed in detail here. This analysis reveals that the crystals undergo remarkable changes following a variety of possible dehydration pathways: some changes occur gradually whilst others are abrupt and require significant domain rearrangements. Comparison of domain arrangements in different crystal forms gives insight into the flexibility of RT which. in turn. may reflect the internal motions allowing this therapeutically important enzyme to fulfill its biological function.