View source for 7wzz


==Crystal structure of peptide KAGQVVTIW in complex with HLA-B5801==
<StructureSection load='7wzz' size='340' side='right'caption='[[7wzz]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7wzz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WZZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WZZ 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]] 1.305&#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></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=7wzz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wzz OCA], [https://pdbe.org/7wzz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wzz RCSB], [https://www.ebi.ac.uk/pdbsum/7wzz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wzz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/F4NC28_HUMAN F4NC28_HUMAN] Involved in the presentation of foreign antigens to the immune system.[ARBA:ARBA00002297]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Allopurinol, widely used in gout treatment, is the most common cause of severe cutaneous adverse drug reactions. The risk of developing such life-threatening reactions is increased particularly for HLA-B*58:01 positive individuals. However the mechanism of action between allopurinol and HLA remains unknown. We demonstrate here that a Lamin A/C peptide KAGQVVTI which is unable to bind HLA-B*58:01 on its own, is enabled to form a stable peptide-HLA complex only in the presence of allopurinol. Crystal structure analysis reveal that allopurinol non-covalently facilitated KAGQVVTI to adopt an unusual binding conformation, whereby the C-terminal isoleucine does not engage as a POmega that typically fit deeply in the binding F-pocket. A similar observation, though to a lesser degree was seen with oxypurinol. Presentation of unconventional peptides by HLA-B*58:01 aided by allopurinol contributes to our fundamental understanding of drug-HLA interactions. The binding of peptides from endogenously available proteins such as self-protein lamin A/C and viral protein EBNA3B suggest that aberrant loading of unconventional peptides in the presence of allopurinol or oxypurinol may be able to trigger anti-self reactions that can lead to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Allopurinol non-covalently facilitates binding of unconventional peptides to HLA-B*58:01.,Huan X, Zhuo N, Lee HY, Ren EC Sci Rep. 2023 Jun 9;13(1):9373. doi: 10.1038/s41598-023-36293-z. PMID:37296297<ref>PMID:37296297</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7wzz" style="background-color:#fffaf0;"></div>

==See Also==
*[[MHC 3D structures|MHC 3D structures]]
*[[MHC I 3D structures|MHC I 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Huan X]]
[[Category: Ren EC]]