Abstract:
Histidine is a very common metal ligand in metalloenzymes. Besides being an efficient Lewis base, its electronic properties are essential to shape the metal ability to catalyze the reaction. Here we show that histidine\'s properties can be tuned, in turn, by an easy proton transfer to a nearby glutamate. We study this situation in Human Carbonic Anhydrase II (HCA II) in which one of the three histidines bound to zinc (His119) interacts also with a glutamate residue (Glu117). Proton transfer from His119 to Glu117 has been hypothesized in the past, however realistic modeling is performed here for the first time. We show that the carboxylate group of Glu117 behaves only as a hydrogen bond acceptor in the hydroxy form of HCA II. On the other hand, our results suggest that Glu117 could exist either as a hydrogen bond acceptor or as a proton acceptor in the aqua form of HCA II, the two isomers having almost the same thermodynamic stability. We propose that this proton shift may be used by the enzyme to facilitate the final displacement of bicarbonate by water.
摘要:
组氨酸是金属酶中非常常见的金属配体。除了是一个高效的刘易斯基地,它的电子特性对于塑造金属催化反应的能力至关重要。在这里,我们表明组氨酸的性质可以调整,反过来,通过简单的质子转移到附近的谷氨酸。我们在人类碳酸酐酶II(HCAII)中研究了这种情况,其中与锌结合的三个组氨酸之一(His119)也与谷氨酸残基(Glu117)相互作用。质子从His119转移到Glu117是过去的假设,然而,真实的建模是第一次在这里进行。我们表明,Glu117的羧酸酯基团仅在HCAII的羟基形式中充当氢键受体。另一方面,我们的结果表明,Glu117可以作为氢键受体或质子受体存在于水性形式的HCAII中,这两种异构体具有几乎相同的热力学稳定性。我们建议酶可以使用这种质子位移来促进水最终置换碳酸氢盐。