A novel catalytic heme cofactor in SfmD with a single thioether bond and a bis -His ligand set revealed by a de novo crystal structural and spectroscopic study

Year: 2021

Type: article

Abstract: , His274 and His313. We demonstrated that SfmD heme is catalytically active and can utilize dioxygen and ascorbate for a single-oxygen insertion into 3-methyl-l-tyrosine. Catalytic assays using ascorbate derivatives revealed the functional groups of ascorbate essential to its function as a cosubstrate. Abolishing the thioether linkage through mutation of Cys317 resulted in catalytically inactive SfmD variants. EPR and optical data revealed that the heme center undergoes a substantial conformational change with one axial histidine ligand dissociating from the iron ion in response to substrate 3-methyl-l-tyrosine binding or chemical reduction by a reducing agent, such as the cosubstrate ascorbate. The labile axial ligand was identified as His274 through redox-linked structural determinations. Together, identifying an unusual heme cofactor with a previously unknown heme-binding motif for a monooxygenase activity and the structural similarity of SfmD to the members of the heme-based tryptophan dioxygenase superfamily will broaden understanding of heme chemistry.

Source: Chemical Science

DOI: 10.1039/d0sc06369j

Authors: Inchul Shin, Ian Davis, Karinel Nieves-Merced, Yifan Wang, Stanton McHardy, Aimin Liu

Institution: The University of Texas at San Antonio

Language: English

Topic: Metal-Catalyzed Oxygenation Mechanisms

Subfield: Inorganic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: diamond

Funders: U.S. Department of Energy, Cancer Prevention and Research Institute of Texas, National Institutes of Health, Office of Science, National Institute of General Medical Sciences, Basic Energy Sciences, Argonne National Laboratory, SLAC National Accelerator Laboratory

OpenAlex ID: W3122977184