View source for 5jtc


==Aspartyl/Asparaginyl beta-hydroxylase (AspH)oxygenase and TPR domains in complex with manganese, 2,4-pyridine dicarboxylate and factor X substrate peptide fragment(39mer-4Ser)==
<StructureSection load='5jtc' size='340' side='right'caption='[[5jtc]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jtc]] is a 2 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=5JTC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JTC 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]] 2.24&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PD2:PYRIDINE-2,4-DICARBOXYLIC+ACID'>PD2</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=5jtc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jtc OCA], [https://pdbe.org/5jtc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jtc RCSB], [https://www.ebi.ac.uk/pdbsum/5jtc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jtc 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human 2-oxoglutarate dependent oxygenase aspartate/asparagine-beta-hydroxylase (AspH) catalyses the hydroxylation of Asp/Asn-residues in epidermal growth factor-like domains (EGFDs). AspH is upregulated on the surface of malign cancer cells; increased AspH levels correlate with tumour invasiveness. Due to a lack of efficient assays to monitor the activity of isolated AspH, there are few reports of studies aimed at identifying small-molecule AspH inhibitors. Recently, it was reported that AspH substrates have a non-canonical EGFD disulfide pattern. Here we report that a stable synthetic thioether mimic of AspH substrates can be employed in solid phase extraction mass spectrometry based high-throughput AspH inhibition assays which are of excellent robustness, as indicated by high Z'-factors and good signal-to-noise/background ratios. The AspH inhibition assay was applied to screen approximately 1500 bioactive small-molecules, including natural products and active pharmaceutical ingredients of approved human therapeutics. Potent AspH inhibitors were identified from both compound classes. Our AspH inhibition assay should enable the development of potent and selective small-molecule AspH inhibitors and contribute towards the development of safer inhibitors for other 2OG oxygenases, e.g. screens of the hypoxia-inducible factor prolyl-hydroxylase inhibitors revealed that vadadustat inhibits AspH with moderate potency.

Aspartate/asparagine-beta-hydroxylase: a high-throughput mass spectrometric assay for discovery of small molecule inhibitors.,Brewitz L, Tumber A, Pfeffer I, McDonough MA, Schofield CJ Sci Rep. 2020 May 26;10(1):8650. doi: 10.1038/s41598-020-65123-9. PMID:32457455<ref>PMID:32457455</ref>

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

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