Jiménez Aurora, Clapés Pere, Crehuet Ramon
Institut de Química Avançada de Catalunya IQAC-CSIC c/Jordi Girona 18-26, 08034, Barcelona, Catalonia, Spain.
Chemistry. 2009;15(6):1422-8. doi: 10.1002/chem.200801223.
The mobility of rhamnulose-1-phosphate aldolase (RhuA) was analysed with a normal mode description and high level calculations on models of the active site. We report the connection between the mobility and the chemical properties of the active site, and compare them to a closely related enzyme, fuculose-1-phosphate aldolase (FucA). Calculations show that the different coordination number for the zinc ion, reported in the crystal structures of RhuA and FucA, was due to a different spatial arrangement of the residues, not to their different chemical nature. Moreover, the metal coordination change is correlated with activity. The domain mobility of the enzyme can reshape the active site of RhuA into the arrangement found in the FucA structure, and vice-versa. This has a direct influence on the energy barrier for the aldol reaction catalyzed by these enzymes, thus showing a coupling of the domain movements and the catalytic effects. Hence domain movements and the coordination chemistry of the active site metal suggest an explanation of why these enzymes have similar experimental turnover rates.
利用正常模式描述和对活性位点模型的高水平计算分析了鼠李糖-1-磷酸醛缩酶（RhuA）的流动性。我们报告了流动性与活性位点化学性质之间的联系，并将它们与一种密切相关的酶——岩藻糖-1-磷酸醛缩酶（FucA）进行比较。计算表明，RhuA和FucA晶体结构中报道的锌离子不同配位数是由于残基的空间排列不同，而非其化学性质不同。此外，金属配位变化与活性相关。酶的结构域流动性可将RhuA的活性位点重塑为FucA结构中的排列，反之亦然。这对这些酶催化的醛醇反应的能垒有直接影响，从而显示出结构域运动与催化效应的耦合。因此，结构域运动和活性位点金属的配位化学解释了为什么这些酶具有相似的实验周转速率。
