Ye Jin, Bazzi Sophia, Fritz Tobias, Tittmann Kai, Mata Ricardo A, Uranga Jon
Institute for Physical Chemistry, Georg-August Universität Göttingen, Tammannstraße 6, D-37077, Göttingen, Germany.
Department of Molecular Enzymology, Göttingen Center of Molecular Biosciences, Georg-August University Göttingen, Göttingen, Germany.
Angew Chem Int Ed Engl. 2023 Sep 4;62(36):e202304163. doi: 10.1002/anie.202304163. Epub 2023 Jul 24.
Recently, a new naturally occurring covalent linkage was characterised, involving a cysteine and a lysine, bridged through an oxygen atom. The latter was dubbed as the NOS bond, reflecting the individual atoms involved in this uncommon bond which finds little parallel in lab chemistry. It is found to form under oxidising conditions and is reversible upon addition of reducing agents. Further studies have identified the bond in crystal structures across a variety of systems and organisms, potentially playing an important role in regulation, cellular defense and replication. Not only that, double NOS bonds have been identified and even found to be competitive in relation to the formation of disulfide bonds. This raises several questions about how this exotic bond comes to be, what are the intermediates involved in its formation and how it competes with other pathways of sulfide oxidation. With this objective in mind, we revisited our first proposed mechanism for the reaction with model electronic structure calculations, adding information about the reactivity with alternative reactive oxygen species and other potential competing products of oxidation. We present a network with more than 30 reactions which provides one of the most encompassing pictures for cysteine oxidation pathways to date.
最近，一种新的天然存在的共价键被表征出来，它涉及一个半胱氨酸和一个赖氨酸，通过一个氧原子桥连。后者被称为NOS键，这反映了参与这种不常见键的各个原子，在实验室化学中几乎找不到类似的情况。已发现它在氧化条件下形成，并且在加入还原剂后是可逆的。进一步的研究已经在各种系统和生物体的晶体结构中鉴定出了这种键，它可能在调节、细胞防御和复制中发挥重要作用。不仅如此，还鉴定出了双NOS键，甚至发现其在二硫键形成方面具有竞争性。这就引发了几个问题：这种奇特的键是如何形成的，其形成过程中涉及哪些中间体，以及它如何与其他硫化物氧化途径竞争。出于这个目的，我们用模型电子结构计算重新审视了我们最初提出的反应机制，增加了与其他活性氧物种以及其他潜在氧化竞争产物反应性的信息。我们展示了一个包含30多个反应的网络，它提供了迄今为止半胱氨酸氧化途径最全面的图景之一。
