Structure and function of heme proteins regulated by diverse post-translational modifications

Abstract

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.

Keywords: Cross-link; Heme proteins; Inhibitors; Post-translational modifications; Protein design.