Work

Fe ion coordination direction and refresh mechanism in off-line αKG-dependent hydroxylase

Year: 2025

Type: article

Abstract: In non-heme iron/α-ketoglutarate (αKG)-dependent enzyme which is one of the main forms of iron present in living organisms, αKG can bind in two different modes, "in-line" and "off-line", depending on the orientation of its C-1 carboxyl. A classical mechanism involving a Fe(IV) = O intermediate has been proposed in in-line enzymes. However, no reasonable catalytic mechanism had been proposed for off-line αKG-dependent enzyme because αKG in this binding mode hinders the activated oxygen on Fe ion from approaching the substrate. In this study, we find the fixed coordination direction of Fe ion and propose a potential catalytic mechanism involving Fe ion release and refresh in non-heme αKG enzymes based on reaction intermediate crystal structures and enzyme assay of UbPH, an off-line αKG dependent trans-L-proline hydroxylase.

Source: International Journal of Biological Macromolecules

DOI: 10.1016/j.ijbiomac.2025.140942

Authors: Yijun Fang, Weimin Gong, Lin Yang

Institution: University of Science and Technology of China

Language: English

Topic: Metal-Catalyzed Oxygenation Mechanisms

Subfield: Inorganic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,390

Funders: National Natural Science Foundation of China, Chinese Academy of Sciences, National Key Research and Development Program of China