5JZU
Aspartyl/Asparaginyl beta-hydroxylase (AspH)oxygenase and TPR domains in complex with manganese, N-oxalylglycine and factor X substrate peptide fragment (26mer)
Summary for 5JZU
| Entry DOI | 10.2210/pdb5jzu/pdb |
| Descriptor | Aspartyl/asparaginyl beta-hydroxylase, Coagulation factor X, MANGANESE (II) ION, ... (5 entities in total) |
| Functional Keywords | 2-oxoglutarate dependent oxygenase, aspartyl/asparaginyl beta-hydroxylase, egf-like domain hydroxylase, double stranded beta-helix, tetratricopeptide repeat, oxidoreductase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 52390.33 |
| Authors | McDonough, M.A.,Pfeffer, I. (deposition date: 2016-05-17, release date: 2017-06-07, Last modification date: 2024-10-23) |
| Primary citation | 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 Cited by 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: 31659163DOI: 10.1038/s41467-019-12711-7 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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