Journal article

Aspartate/asparagine-β-hydroxylase crystal structures reveal an unexpected epidermal growth factor-like domain substrate disulfide pattern.

Inga Pfeffer, Lennart Brewitz, Tobias Krojer, Sacha A Jensen, Grazyna T Kochan, Nadia J Kershaw, Kirsty S Hewitson, Luke A McNeill, Holger Kramer, Martin Münzel, Richard J Hopkinson, Udo Oppermann, Penny A Handford, Michael A McDonough, Christopher J Schofield

Nature Communications | Published : 2019

Abstract

AspH is an endoplasmic reticulum (ER) membrane-anchored 2-oxoglutarate oxygenase whose C-terminal oxygenase and tetratricopeptide repeat (TPR) domains present in the ER lumen. AspH catalyses hydroxylation of asparaginyl- and aspartyl-residues in epidermal growth factor-like domains (EGFDs). Here we report crystal structures of human AspH, with and without substrate, that reveal substantial conformational changes of the oxygenase and TPR domains during substrate binding. Fe(II)-binding by AspH is unusual, employing only two Fe(II)-binding ligands (His679/His725). Most EGFD structures adopt an established fold with a conserved Cys1-3, 2-4, 5-6 disulfide bonding pattern; an unexpected Cys3-4 di..

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University of Melbourne Researchers