Unusual Self-Hydroxylation in 4-Histidine Tetrad-Supporting Nonheme Iron Center.
Fujieda, N., Ishihama, K.I., Ichihashi, H., Yanagisawa, S., Kurisu, G., Itoh, S.(2025) Chem Asian J : e202401191-e202401191
- PubMed: 40260495 
- DOI: https://doi.org/10.1002/asia.202401191
- Primary Citation of Related Structures:  
9JET, 9JEU, 9JEV, 9JEW - PubMed Abstract: 
The TM1459 protein from Thermotoga maritima is a member of the cupin protein superfamily and contains a mononuclear metal center. Structural information has been obtained using X-ray crystallography; however, its physiological role remains unknown. The metal-binding site has an octahedral coordination geometry ligated by four histidine imidazoles and two terminal water molecules present in the cis position. This protein had the ability to bind Mn, Fe, and Zn ions; additionally, a self-hydroxylation reaction occurred in the Fe-TM1459 C106V mutant. Namely, one of the tyrosine residues (Tyr7) was hydroxylated to generate the green form. Spectroscopic analyses using Vis-NIR, MALDI-TOF/MS, and resonance Raman spectroscopy confirmed that Tyr7 was hydroxylated to 3,4-dihydroxyphenylalanine giving an iron-catecholate complex. Because the Y7A/C106V mutant did not produce this green form, the mutation of Cys106 to Val was assumed to have induced a conformational change in Tyr7 that facilitated its approach to the metal center promoting the self-hydroxylation reaction. Thus, these results demonstrated that Fe-TM1459 protein has monooxygenase activity.
Organizational Affiliation: 
Department of Applied Biological Chemistry, Graduate School of Agriculture, Osaka Metropolitan University, 1-1 Gakuen-cho, Naka-ku, Sakai-shi, Osaka, 599-8531, Japan.