Abstract：
As(III) S-adenosylmethionine methyltransferases, pivotal enzymes in arsenic metabolism, facilitate the methylation of arsenic up to three times. This process predominantly yields trivalent mono- and dimethylarsenite, with trimethylarsine forming in smaller amounts. While this enzyme acts as a detoxifier in microbial systems by altering As(III), in humans, it paradoxically generates more toxic and potentially carcinogenic methylated arsenic species. The strong affinity of As(III) for cysteine residues, forming As(III)-thiolate bonds, is exploited in medical treatments, notably in arsenic trioxide (Trisenox®), an FDA-approved drug for leukemia. The effectiveness of this drug is partly due to its interaction with cysteine residues, leading to the breakdown of key oncogenic fusion proteins. In this study, we extend the understanding of As(III)\'s binding mechanisms, showing that, in addition to As(III)-S covalent bonds, noncovalent O⋅⋅⋅As pnictogen bonding plays a vital role. This interaction significantly contributes to the structural stability of the As(III) complexes. Our crystallographic analysis using the PDB database of As(III) S-adenosylmethionine methyltransferases, augmented by comprehensive theoretical studies including molecular electrostatic potential (MEP), quantum theory of atoms in molecules (QTAIM), and natural bond orbital (NBO) analysis, emphasizes the critical role of pnictogen bonding in these systems. We also undertake a detailed evaluation of the energy characteristics of these pnictogen bonds using various theoretical models. To our knowledge, this is the first time pnictogen bonds in As(III) derivatives have been reported in biological systems, marking a significant advancement in our understanding of arsenic\'s molecular interactions.
摘要：
作为（III）S-腺苷甲硫氨酸甲基转移酶，砷代谢中的关键酶，促进砷的甲基化达三倍。该过程主要产生三价单亚砷酸盐和二甲基亚砷酸盐，与三甲基砷化氢形成较少量。As（III）对半胱氨酸残基的强亲和力，形成As(III)-硫醇盐键，在医疗中被利用。在这项研究中,我们扩展了对As(III)约束机制的理解，证明这一点，除了As(III)-S共价键，非共价O···由于pnictogen键起着至关重要的作用。这种相互作用显著有助于As(III)配合物的结构稳定性。我们使用As（III）S-腺苷甲硫氨酸甲基转移酶的PDB数据库进行晶体学分析，通过全面的理论研究，包括分子静电势(MEP)，分子中原子的量子理论(QTAIM)，和自然键轨道(NBO)分析，强调了pnictogen键合在这些系统中的关键作用。我们还使用各种理论模型对这些pnictogen键的能量特性进行了详细的评估。据我们所知,这是首次在生物系统中报道As（III）衍生物中的pnictogen键，标志着我们对砷分子相互作用的理解有了显著的进步。
