INRS - Institut Armand Frappier, Université du Québec, 531 Boulevard des Prairies, Laval, QC, H7V 1B7, Canada.
Structural Biology Initiative, CUNY Advanced Science Research Center, New York, NY, USA.
Sci Rep. 2017 Jun 9;7(1):3207. doi: 10.1038/s41598-017-03298-4.
In this work, we applied the sequence-based statistical coupling analysis approach to characterize conserved amino acid networks important for biochemical function in the pancreatic-type ribonuclease (ptRNase) superfamily. This superfamily-wide analysis indicates a decomposition of the RNase tertiary structure into spatially distributed yet physically connected networks of co-evolving amino acids, termed sectors. Comparison of this statistics-based description with new NMR experiments data shows that discrete amino acid networks, termed sectors, control the tuning of distinct functional properties in different enzyme homologs. Further, experimental characterization of evolutionarily distant sequences reveals that sequence variation at sector positions can distinguish homologs with a conserved dynamic pattern and optimal catalytic activity from those with altered dynamics and diminished catalytic activities. Taken together, these results provide important insights into the mechanistic design of the ptRNase superfamily, and presents a structural basis for evolutionary tuning of function in functionally diverse enzyme homologs.
在这项工作中，我们应用基于序列的统计耦合分析方法来描述对胰腺型核糖核酸酶（ptRNase）超家族中生化功能重要的保守氨基酸网络。这项全超家族分析表明，核糖核酸酶的三级结构可以分解为空间分布但物理上连接的共进化氨基酸网络，称为扇区。将这种基于统计的描述与新的 NMR 实验数据进行比较表明，离散的氨基酸网络，称为扇区，控制着不同酶同系物中不同功能特性的调谐。此外，对进化上差异较大的序列的实验表征表明，扇区位置的序列变异可以区分具有保守动力学模式和最佳催化活性的同系物与具有改变的动力学和降低的催化活性的同系物。总之，这些结果为 ptRNase 超家族的机械设计提供了重要的见解，并为功能多样的酶同系物中功能进化的调节提供了结构基础。
