Human oxygenase variants employing a single protein Fe(II) ligand are catalytically active

Journal article

Aspartate/asparagine-β-hydroxylase (AspH) is a human 2-oxoglutarate (2OG) and Fe^II oxygenase that catalyses C3 hydroxylations of aspartate/asparagine residues of epidermal growth factor-like domains (EGFDs). Unusually, AspH employs two histidine residues to chelate Fe^II rather than the typical triad of two histidine and one glutamate/aspartate residue. We report kinetic, inhibition, and crystallographic studies concerning human AspH variants in which either of its Fe^II binding histidine residues are substituted for alanine. Both the H725A and, in particular, the H679A AspH variants retain substantial catalytic activity. Crystal structures clearly reveal metal-ligation by only a single protein histidine ligand. The results have implications for the functional assignment of 2OG oxygenases and for the design of non-protein biomimetic catalysts.

Authors: Brasnett, A; Pfeffer, I; Brewitz, L; Chowdhury, R; Nakashima, Y

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Angewandte Chemie International Edition
• Volume: 60
• Issue: 26
• Pages: 14657-14663
• Publication date: 2021-05-19
• Acceptance date: 2021-04-15
• DOI: 10.1002/anie.202103711
• EISSN: 1521-3773
• ISSN: 1433-7851
• Language: English
• Keywords: FFR