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Human oxygenase variants employing a single protein Fe(II) ligand are catalytically active
Authors:
Amelia
Brasnett
(University of Oxford)
,
Inga
Pfeffer
(University of Oxford)
,
Lennart
Brewitz
(University of Oxford)
,
Rasheduzzaman
Chowdhury
(University of Oxford)
,
Yu
Nakashima
(University of Oxford)
,
Anthony
Tumber
(University of Oxford)
,
Michael A.
Mcdonough
(University of Oxford)
,
Christopher
Schofield
(University of Oxford)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Angewandte Chemie International Edition
State:
Published (Approved)
Published:
April 2021

Abstract: Aspartate/asparagine‐β‐hydroxylase (AspH) is a human 2‐oxoglutarate (2OG) and Fe(II) oxygenase that catalyzes 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 variant 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.
Journal Keywords: Aspartate/asparagine-β-hydroxylase/AspH/BAH/HAAH; 2-oxoglutarate/α-ketoglutarate oxygenase; biomimetic catalysis; Fe(II) binding metallo-enzymes; Epigenetics
Diamond Keywords: Epigenetics; Enzymes
Subject Areas:
Biology and Bio-materials,
Chemistry
Instruments:
I03-Macromolecular Crystallography
,
I04-Macromolecular Crystallography
Added On:
26/04/2021 13:17
Documents:
anie.202103711.pdf
Discipline Tags:
Biochemistry
Genetics
Catalysis
Chemistry
Structural biology
Organic Chemistry
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)