Exploring Local Flexibility/Rigidity in Psychrophilic and Mesophilic Carbonic Anhydrases
Exploring Local Flexibility/Rigidity in Psychrophilic and Mesophilic Carbonic Anhydrases
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DOI：
10.1016/j.bpj.2008.11.017
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发表时间：
2009-02-18
影响因子：
3.4
通讯作者：
Pompa, P. P.
中科院分区：
文献类型：
--
作者：
Chiuri, R.;Maiorano, G.;Pompa, P. P.
蛋白质分子的功能和特异性需要分子的柔性和刚性。一些嗜冷酶在低温下表现出更高的催化效率，与它们的中/嗜热同源物所表现出的效率相比。新出现的图片表明，这种酶具有更好的灵活性的结构催化成分，而其他蛋白质区域远离功能位点可能比他们的嗜温同行更刚性。为了更深入地分析蛋白质结构中的活性-柔性/刚性关系，通过荧光研究、三维建模和活性分析，将南极硬骨鱼Chionodraco hamatus的嗜冷碳酸酐酶与牛的碳酸酐酶11进行了比较。数据表明，冷适应的酶表现出在低温和中等温度下的催化效率增加，更有趣的是，在控制催化结构的正确折叠的区域中的局部灵活性，以及在疏水核心中的刚性。在嗜温对应物中观察到相反的结果。这些结果表明，灵活和刚性的蛋白质亚结构，可能是有用的一类酶在病理过程中发挥关键作用的合理的分子和药物设计的活性和存在之间的明确关系。
Molecular flexibility and rigidity are required to determine the function and specificity of protein molecules. Some psychrophilic enzymes demonstrate a higher catalytic efficiency at low temperatures, compared to the efficiency demonstrated by their meso/thermophilic homologous. The emerging picture suggests that such enzymes have an improved flexibility of the structural catalytic components, whereas other protein regions far from functional sites may be even more rigid than those of their mesophilic counterparts. To gain a deeper insight in the analysis of the activity-flexibility/rigidity relationship in protein structure, psychrophilic carbonic anhydrase of the Antarctic teleost Chionodraco hamatus has been compared with carbonic anhydrase 11 of Bos taurus through fluorescence studies, three-dimensional modeling, and activity analyses. Data demonstrated that the cold-adapted enzyme exhibits an increased catalytic efficiency at low and moderate temperatures and, more interestingly, a local flexibility in the region that controls the correct folding of the catalytic architecture, as well as a rigidity in the hydrophobic; core. The opposite result was observed in the mesophilic counterpart. These results suggest a clear relationship between the activity and the presence of flexible and rigid protein substructures that may be useful in rational molecular and drug design of a class of enzymes playing a key role in pathologic processes.