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| | <StructureSection load='5apa' size='340' side='right'caption='[[5apa]], [[Resolution|resolution]] 2.05Å' scene=''> | | <StructureSection load='5apa' size='340' side='right'caption='[[5apa]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5apa]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3rcq 3rcq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5APA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5APA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5apa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3rcq 3rcq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5APA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5APA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LMR:(2S)-2-HYDROXYBUTANEDIOIC+ACID'>LMR</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LMR:(2S)-2-HYDROXYBUTANEDIOIC+ACID'>LMR</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptide-aspartate_beta-dioxygenase Peptide-aspartate beta-dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.16 1.14.11.16] </span></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=5apa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5apa OCA], [https://pdbe.org/5apa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5apa RCSB], [https://www.ebi.ac.uk/pdbsum/5apa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5apa ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5apa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5apa OCA], [http://pdbe.org/5apa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5apa RCSB], [http://www.ebi.ac.uk/pdbsum/5apa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5apa ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Peptide-aspartate beta-dioxygenase]]
| + | [[Category: Allerston C]] |
| - | [[Category: Allerston, C]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Bountra C]] |
| - | [[Category: Bountra, C]] | + | [[Category: Chaikuad A]] |
| - | [[Category: Chaikuad, A]] | + | [[Category: Edwards A]] |
| - | [[Category: Delft, F von]]
| + | [[Category: Gileadi O]] |
| - | [[Category: Edwards, A]] | + | [[Category: Hozjan V]] |
| - | [[Category: Gileadi, O]] | + | [[Category: Kavanagh K]] |
| - | [[Category: Hozjan, V]] | + | [[Category: Kochan G]] |
| - | [[Category: Kavanagh, K]] | + | [[Category: Krojer T]] |
| - | [[Category: Kochan, G]] | + | [[Category: McDonough MA]] |
| - | [[Category: Krojer, T]] | + | [[Category: Muniz JR]] |
| - | [[Category: McDonough, M A]] | + | [[Category: Oppermann U]] |
| - | [[Category: Muniz, J R]] | + | [[Category: Pfeffer I]] |
| - | [[Category: Oppermann, U]] | + | [[Category: Pilka E]] |
| - | [[Category: Pfeffer, I]] | + | [[Category: Weigelt J]] |
| - | [[Category: Pilka, E]] | + | [[Category: Von Delft F]] |
| - | [[Category: Weigelt, J]] | + | |
| - | [[Category: Oxidoreductase]] | + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| Structural highlights
Function
ASPH_HUMAN Isoform 1: specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins.[1] 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.[2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Srikanth S, Jew M, Kim KD, Yee MK, Abramson J, Gwack Y. Junctate is a Ca2+-sensing structural component of Orai1 and stromal interaction molecule 1 (STIM1). Proc Natl Acad Sci U S A. 2012 May 29;109(22):8682-7. doi:, 10.1073/pnas.1200667109. Epub 2012 May 14. PMID:22586105 doi:10.1073/pnas.1200667109
- ↑ Srikanth S, Jew M, Kim KD, Yee MK, Abramson J, Gwack Y. Junctate is a Ca2+-sensing structural component of Orai1 and stromal interaction molecule 1 (STIM1). Proc Natl Acad Sci U S A. 2012 May 29;109(22):8682-7. doi:, 10.1073/pnas.1200667109. Epub 2012 May 14. PMID:22586105 doi:10.1073/pnas.1200667109
- ↑ 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. Aspartate/asparagine-beta-hydroxylase crystal structures reveal an unexpected epidermal growth factor-like domain substrate disulfide pattern. Nat Commun. 2019 Oct 28;10(1):4910. doi: 10.1038/s41467-019-12711-7. PMID:31659163 doi:http://dx.doi.org/10.1038/s41467-019-12711-7
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