School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China; Laboratory of Protein Structure and Function, University of South China, Hengyang 421001, China.
Arch Biochem Biophys. 2018 Mar 1;641:1-30. doi: 10.1016/j.abb.2018.01.009. Epub 2018 Feb 2.
Heme proteins are crucial for biological systems by performing diverse functions. Nature has evolved diverse approaches to fine-tune the structure and function of heme proteins, of which post-translational modification (PTM) is a primary method. As reviewed herein, a multitude of PTMs have been discovered for heme proteins in the last several decades, including heme-protein cross-links with heme side chains (Cys-heme, Tyr-heme and Asp/Glu-heme, etc) or porphyrin ring (Lys-heme and Tyr-heme, etc), heme modifications (sulfheme and nitriheme, etc), amino acids cross-links between two or among multiple residues (Cys-Cys, Tyr-His, Tyr-Cys, Met-Tyr-Trp, etc), and amino acids modifications by oxidation, nitration, phosphorylation and glycation, etc. With the development of research methods and advances in research techniques, deep insights have been obtained for the formation mechanisms of PTMs, as well as their effects on the structure and function of heme proteins. Moreover, some positive PTMs have been successfully applied to create artificial heme proteins with advanced functions, whereas some negative PTMs have been regulated by rational design of inhibitors. The tremendous progress, together with those ongoing, will make it possible to rationally control the diverse PTMs of heme proteins, especially those associated with human diseases, toward our desired goals for a better life.
血红素蛋白通过执行多种功能对生物系统至关重要。大自然已经进化出多种方法来微调血红素蛋白的结构和功能，其中翻译后修饰（PTM）是主要方法。本文综述了过去几十年中发现的大量血红素蛋白 PTM，包括血红素侧链（半胱氨酸-血红素、酪氨酸-血红素和天冬氨酸/谷氨酸-血红素等）或卟啉环（赖氨酸-血红素和酪氨酸-血红素等）与血红素蛋白的交联、血红素修饰（亚硫酸血红素和硝酰血红素等）、两个或多个残基之间的氨基酸交联（半胱氨酸-半胱氨酸、酪氨酸-组氨酸、酪氨酸-半胱氨酸、甲硫氨酸-色氨酸-色氨酸等）以及氨基酸的氧化、硝化、磷酸化和糖化等修饰。随着研究方法的发展和研究技术的进步，人们对 PTM 的形成机制及其对血红素蛋白结构和功能的影响有了更深入的了解。此外，一些积极的 PTM 已成功应用于创建具有先进功能的人工血红素蛋白，而一些消极的 PTM 已通过抑制剂的合理设计进行了调控。这些巨大的进展以及正在进行的研究，将使我们有可能对血红素蛋白的各种 PTM 进行合理控制，特别是那些与人类疾病相关的 PTM，以实现我们对美好生活的期望。
