The X-ray crystal structure of human A15C neuroglobin reveals both native/de novo disulfide bonds and unexpected ligand-binding sites

Human neuroglobin (Ngb) contains a heme group and three Cys residues (Cys46, Cys55, and Cys120) in the polypeptide chain. By introducing an additional Cys at position 15, the X-ray structure of A15C Ngb mutant was solved at a high resolution of 1.35 angstrom, which reveals the formation of both the native (C46-C55) and the engineered (C15-C120) disulfide bonds, likely playing a functional and structural role, respectively, according to the geometry analysis. Unexpectedly, 1,4-dioxane from the crystallization reagents was bound not only to the protein surface, but also to the heme distal pocket, providing insights into protein-ligand interactions for the globin and guiding the design of functional heme enzymes.

Automated summary

This study elucidates the structure and function of human neuroglobin. By introducing an additional Cys residue, it was found that two disulfide bonds are formed. The binding of 1,4-dioxane from the crystallization reagents to both the protein and heme provides insights into protein-ligand interactions and guides the design of functional heme enzymes.