REQUIMTE/Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
J Theor Biol. 2010 Dec 7;267(3):388-95. doi: 10.1016/j.jtbi.2010.09.012. Epub 2010 Sep 16.
Throughout evolution, mutations in particular regions of some protein structures have resulted in extra covalent bonds that increase the overall robustness of the fold: disulfide bonds. The two strategically placed cysteines can also have a more direct role in protein function, either by assisting thiol or disulfide exchange, or through allosteric effects. In this work, we verified how the structural similarities between disulfides can reflect functional and evolutionary relationships between different proteins. We analyzed the conformational patterns of the disulfide bonds in a set of disulfide-rich proteins that included twelve SCOP superfamilies: thioredoxin-like and eleven superfamilies containing small disulfide-rich proteins (SDP).
The twenty conformations considered in the present study were characterized by both structural and energetic parameters. The corresponding frequencies present diverse patterns for the different superfamilies. The least-strained conformations are more abundant for the SDP superfamilies, while the "catalytic" +/-RHook is dominant for the thioredoxin-like superfamily. The "allosteric" -RHSaple is moderately abundant for BBI, Crisp and Thioredoxin-like superfamilies and less frequent for the remaining superfamilies. Using a hierarchical clustering analysis we found that the twelve superfamilies were grouped in biologically significant clusters.
In this work, we carried out an extensive statistical analysis of the conformational motifs for the disulfide bonds present in a set of disulfide-rich proteins. We show that the conformational patterns observed in disulfide bonds are sufficient to group proteins that share both functional and structural patterns and can therefore be used as a criterion for protein classification.
在进化过程中，某些蛋白质结构特定区域的突变会导致额外的共价键，从而提高折叠的整体稳定性：二硫键。两个位置巧妙的半胱氨酸也可以在蛋白质功能中发挥更直接的作用，无论是通过辅助巯基或二硫键交换，还是通过变构效应。在这项工作中，我们验证了二硫键之间的结构相似性如何反映不同蛋白质之间的功能和进化关系。我们分析了一组富含二硫键的蛋白质中二硫键的构象模式，其中包括十二个 SCOP 超家族：硫氧还蛋白样和包含 11 个小富含二硫键蛋白（SDP）的超家族。
本研究考虑的二十种构象由结构和能量参数来表征。不同超家族的对应频率呈现出不同的模式。对于 SDP 超家族，最不紧张的构象更为丰富，而“催化” +/-RHook 对于硫氧还蛋白样超家族则占主导地位。“变构” -RHSaple 在 BBI、Crisp 和硫氧还蛋白样超家族中含量适中，而在其余超家族中则较少。使用层次聚类分析，我们发现这 12 个超家族被分为具有生物学意义的聚类。
在这项工作中，我们对一组富含二硫键的蛋白质中二硫键的构象基元进行了广泛的统计分析。我们表明，观察到的二硫键构象模式足以将具有相似功能和结构模式的蛋白质进行分组，因此可以用作蛋白质分类的标准。
