The photochemistry of cobalamins has recently been found to have biological importance, with the discovery of bacterial photoreceptor proteins, such as CarH and AerR. CarH and AerR, are involved in the light regulation of carotenoid biosynthesis and bacteriochlorophyll biosynthesis, respectively, in bacteria. Experimental transient absorption spectroscopic studies have indicated unusual photochemical behavior of 5′-deoxy-5′-adenosylcobalamin (AdoCbl) in CarH, with excited-state charge separation between cobalt and adenosyl and possible heterolytic cleavage of the Co-adenosyl bond, as opposed to the homolytic cleavage observed in aqueous solution and in many AdoCbl-based enzymes. We employ molecular dynamics and hybrid quantum mechanical/molecular mechanical calculations to obtain a microscopic understanding of the modulation of the excited electronic states of AdoCbl by the CarH protein environment, in contrast to aqueous solution and AdoCbl-based enzymes. Our results indicate a progressive stabilization of the electronic states involving charge transfer (CT) from cobalt/corrin to adenine on changing the environment from gas phase to water to solvated CarH. The solvent exposure of the adenosyl ligand in CarH, the π-stacking interaction between a tryptophan and the adenine moiety, and the hydrogen-bonding interaction between a glutamate and the lower axial ligand of cobalt are found to contribute to the stabilization of the states involving CT to adenine. The combination of these three factors, the latter two of which can be experimentally tested via mutagenesis studies, is absent in an aqueous solvent environment and in AdoCbl-based enzymes. The favored CT from metal and/or corrin to adenine in CarH may promote heterolytic cleavage of the cobalt-adenosyl bond proposed by experimental studies. Overall, this work provides novel, to our knowledge, physical insights into the mechanism of CarH function and directions for future experimental investigations. The fundamental understanding of the mechanism of CarH functioning will serve the development of optogenetic tools based on the new class of B₁₂-dependent photoreceptors.

最近发现钴胺素的光化学具有生物学重要性，发现了细菌感光蛋白，例如 CarH 和 AerR。CarH 和 AerR 分别参与细菌中类胡萝卜素生物合成和细菌叶绿素生物合成的光调节。实验性瞬态吸收光谱研究表明，CarH 中的 5'-deoxy-5'-adenosylcobalamin (AdoCbl) 具有不寻常的光化学行为，钴和腺苷之间存在激发态电荷分离，并且 Co-腺苷键可能发生异裂。在水溶液和许多基于 AdoCbl 的酶中观察到均裂。与水溶液和基于 AdoCbl 的酶相比，我们采用分子动力学和混合量子力学/分子力学计算来获得对 CarH 蛋白环境对 AdoCbl 激发电子态的调制的微观理解。我们的结果表明，在将环境从气相变为水再到溶剂化 CarH 时，涉及从钴/corrin 到腺嘌呤的电荷转移 (CT) 的电子态逐渐​​稳定。CarH中腺苷配体的溶剂暴露，我们的结果表明，在将环境从气相变为水再到溶剂化 CarH 时，涉及从钴/corrin 到腺嘌呤的电荷转移 (CT) 的电子态逐渐​​稳定。CarH中腺苷配体的溶剂暴露，我们的结果表明，在将环境从气相变为水再到溶剂化 CarH 时，涉及从钴/corrin 到腺嘌呤的电荷转移 (CT) 的电子态逐渐​​稳定。CarH中腺苷配体的溶剂暴露，π发现色氨酸和腺嘌呤部分之间的堆积相互作用，以及谷氨酸和钴的下轴配体之间的氢键相互作用有助于稳定涉及 CT 到腺嘌呤的状态。这三个因素的组合，其中后两个可以通过诱变研究进行实验测试，在水性溶剂环境和基于 AdoCbl 的酶中不存在。CarH中从金属和/或corrin到腺嘌呤的首选CT可能促进实验研究提出的钴-腺苷键的异裂切割。总的来说，据我们所知，这项工作为 CarH 功能的机制和未来实验研究的方向提供了新颖的物理见解。₁₂依赖性光感受器。