5JZ8

Aspartyl/Asparaginyl beta-hydroxylase (AspH)oxygenase and TPR domains in complex with manganese, N-oxalylglycine, and factor X substrate peptide fragment (39mer)

5JZ8 の概要

• エントリーDOI: 10.2210/pdb5jz8/pdb
• 分子名称: Aspartyl/asparaginyl beta-hydroxylase, Coagulation factor X, MANGANESE (II) ION, ... (6 entities in total)
• 機能のキーワード: 2-oxoglutarate dependent oxygenase, aspartyl/asparaginyl beta-hydroxylase, egf-like domain hydroxylase, double stranded beta-helix, tetratricopeptide repeat, oxidoreductase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53921.05

構造登録者

McDonough, M.A.,Pfeffer, I. (登録日: 2016-05-16, 公開日: 2017-05-24, 最終更新日: 2024-01-10)

主引用文献

Pfeffer, I.,Brewitz, L.,Krojer, T.,Jensen, S.A.,Kochan, G.T.,Kershaw, N.J.,Hewitson, K.S.,McNeill, L.A.,Kramer, H.,Munzel, M.,Hopkinson, R.J.,Oppermann, U.,Handford, P.A.,McDonough, M.A.,Schofield, C.J.
Aspartate/asparagine-beta-hydroxylase crystal structures reveal an unexpected epidermal growth factor-like domain substrate disulfide pattern.
Nat Commun, 10:4910-4910, 2019

PubMed 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 disulfide bonding pattern is observed in AspH-EGFD substrate complexes, the catalytic relevance of which is supported by studies involving stable cyclic peptide substrate analogues and by effects of Ca(II) ions on activity. The results have implications for EGFD disulfide pattern processing in the ER and will enable medicinal chemistry efforts targeting human 2OG oxygenases.

PubMed: 31659163
DOI: 10.1038/s41467-019-12711-7

実験手法

X-RAY DIFFRACTION (2.095 Å)