View source for 5jza


==Aspartyl/Asparaginyl beta-hydroxylase (AspH)oxygenase and TPR domains in complex with manganese and N-oxalylglycine==
<StructureSection load='5jza' size='340' side='right'caption='[[5jza]], [[Resolution|resolution]] 2.14&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jza]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JZA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JZA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.14&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5jza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jza OCA], [https://pdbe.org/5jza PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jza RCSB], [https://www.ebi.ac.uk/pdbsum/5jza PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jza ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ASPH_HUMAN ASPH_HUMAN] Isoform 1: specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins.<ref>PMID:22586105</ref>   Isoform 8: membrane-bound Ca(2+)-sensing protein, which is a structural component of the ER-plasma membrane junctions. Isoform 8 regulates the activity of Ca(+2) released-activated Ca(+2) (CRAC) channels in T-cells.<ref>PMID:22586105</ref> 
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== Publication Abstract from PubMed ==
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.

Aspartate/asparagine-beta-hydroxylase crystal structures reveal an unexpected epidermal growth factor-like domain substrate disulfide pattern.,Pfeffer I, Brewitz L, Krojer T, Jensen SA, Kochan GT, Kershaw NJ, Hewitson KS, McNeill LA, Kramer H, Munzel M, Hopkinson RJ, Oppermann U, Handford PA, McDonough MA, Schofield CJ Nat Commun. 2019 Oct 28;10(1):4910. doi: 10.1038/s41467-019-12711-7. PMID:31659163<ref>PMID:31659163</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5jza" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hydroxylases 3D structures|Hydroxylases 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: McDonough MA]]
[[Category: Pfeffer I]]