Human Oxygenase Variants Employing a Single Protein FeII Ligand Are Catalytically Active.
Angew Chem Weinheim Bergstr Ger
; 133(26): 14778-14784, 2021 Jun 21.
Article
in En
| MEDLINE
| ID: mdl-38505373
ABSTRACT
Aspartate/asparagine-ß-hydroxylase (AspH) is a human 2-oxoglutarate (2OG) and FeII oxygenase that catalyses C3 hydroxylations of aspartate/asparagine residues of epidermal growth factor-like domains (EGFDs). Unusually, AspH employs two histidine residues to chelate FeII 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 FeII 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Angew Chem Weinheim Bergstr Ger
Journal subject:
BIOFISICA
/
QUIMICA
Year:
2021
Document type:
Article