Zhang Sixue, Stevens David R, Goyal Puja, Bingaman Jamie L, Bevilacqua Philip C, Hammes-Schiffer Sharon
Department of Chemistry, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801-3364, United States.
J Phys Chem Lett. 2016 Oct 6;7(19):3984-3988. doi: 10.1021/acs.jpclett.6b01854. Epub 2016 Sep 28.
Ribozymes employ diverse catalytic strategies in their self-cleavage mechanisms, including the use of divalent metal ions. This work explores the effects of Mg ions in the active site of the glmS ribozyme-GlcN6P cofactor complex using computational methods. Deleterious and potentially beneficial effects of an active site Mg ion on the self-cleavage reaction were identified. The presence of a Mg ion near the scissile phosphate oxygen atoms at the cleavage site was determined to be deleterious, and thereby anticatalytic, due to electrostatic repulsion of the cofactor, disruption of key hydrogen-bonding interactions, and obstruction of nucleophilic attack. On the other hand, the presence of a Mg ion at another position in the active site, the Hoogsteen face of the putative base, was found to avoid these deleterious effects and to be potentially catalytically favorable owing to the stabilization of negative charge and pK shifting of the guanine base.
核酶在其自我切割机制中采用多种催化策略，包括使用二价金属离子。这项工作使用计算方法探索了Mg离子在glmS核酶 - GlcN6P辅因子复合物活性位点中的作用。确定了活性位点Mg离子对自我切割反应的有害和潜在有益影响。由于辅因子的静电排斥、关键氢键相互作用的破坏以及亲核攻击的阻碍，在切割位点的可切割磷酸氧原子附近存在Mg离子被确定为有害的，从而具有抗催化作用。另一方面，在活性位点的另一个位置，即假定碱基的Hoogsteen面，发现存在Mg离子可避免这些有害影响，并且由于鸟嘌呤碱基的负电荷稳定和pK值变化而可能在催化上有利。
