6mjq: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 1: Line 1:
'''Unreleased structure'''


The entry 6mjq is ON HOLD  until Paper Publication
==Crystal structure of the mCD1d/xxp (JJ295) /iNKTCR ternary complex==
<StructureSection load='6mjq' size='340' side='right' caption='[[6mjq]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6mjq]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MJQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MJQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JUD:N-{(2S,3S,4R)-3,4-dihydroxy-1-[(4-O-{[4-(trifluoromethyl)phenyl]methyl}-alpha-D-galactopyranosyl)oxy]octadecan-2-yl}hexacosanamide'>JUD</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6mjq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mjq OCA], [http://pdbe.org/6mjq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mjq RCSB], [http://www.ebi.ac.uk/pdbsum/6mjq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mjq ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/B2MG_MOUSE B2MG_MOUSE]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Invariant natural killer T-cells (iNKT) are a glycolipid-responsive subset of T-lymphocytes that fulfill a pivotal role in the immune system. The archetypical synthetic glycolipid, alpha-galactosylceramide (alpha-GalCer), whose molecular framework is inspired by a group of amphiphilic natural products, remains the most studied antigen for iNKT-cells. Nonetheless, the potential of alpha-GalCer as an immunostimulating agent is compromised by the fact that this glycolipid elicits simultaneous secretion of Th1- and Th2-cytokines. This has incited medicinal chemistry efforts to identify analogues that are able to perturb the Th1/Th2 balance. In this work, we present the synthesis of an extensive set of 4"-O-alkylated alpha-GalCer analogues, which were evaluated in vivo for their cytokine induction. We have found that conversion of the 4"-OH group to ether moieties decreases the immunogenic potential in mice relative to alpha-GalCer. Yet, the benzyl-modified glycolipids are able to produce a distinct pro-inflammatory immune response. The crystal structures suggest an extra hydrophobic interaction between the benzyl moiety and the alpha2-helix of CD1d.


Authors: Zajonc, D.M., Bitra, A., Janssens, J.
4"-O-Alkylated alpha-Galactosylceramide Analogues as iNKT-Cell Antigens: Synthetic, Biological, and Structural Studies.,Janssens J, Bitra A, Wang J, Decruy T, Venken K, van der Eycken J, Elewaut D, Zajonc DM, van Calenbergh S ChemMedChem. 2019 Jan 8;14(1):147-168. doi: 10.1002/cmdc.201800649. Epub 2018 Dec, 17. PMID:30556652<ref>PMID:30556652</ref>


Description: Crystal structure of the mCD1d/xxp (JJ295) /iNKTCR ternary complex
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 6mjq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bitra, A]]
[[Category: Janssens, J]]
[[Category: Janssens, J]]
[[Category: Bitra, A]]
[[Category: Zajonc, D M]]
[[Category: Zajonc, D.M]]
[[Category: Glycolipid antigen presentation]]
[[Category: Ig-fold]]
[[Category: Immune system]]
[[Category: Immune system-inhibitor complex]]
[[Category: Mhc-fold]]
[[Category: T cell receptor]]

Revision as of 09:39, 9 January 2019

Crystal structure of the mCD1d/xxp (JJ295) /iNKTCR ternary complexCrystal structure of the mCD1d/xxp (JJ295) /iNKTCR ternary complex

Structural highlights

6mjq is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.

Publication Abstract from PubMed

Invariant natural killer T-cells (iNKT) are a glycolipid-responsive subset of T-lymphocytes that fulfill a pivotal role in the immune system. The archetypical synthetic glycolipid, alpha-galactosylceramide (alpha-GalCer), whose molecular framework is inspired by a group of amphiphilic natural products, remains the most studied antigen for iNKT-cells. Nonetheless, the potential of alpha-GalCer as an immunostimulating agent is compromised by the fact that this glycolipid elicits simultaneous secretion of Th1- and Th2-cytokines. This has incited medicinal chemistry efforts to identify analogues that are able to perturb the Th1/Th2 balance. In this work, we present the synthesis of an extensive set of 4"-O-alkylated alpha-GalCer analogues, which were evaluated in vivo for their cytokine induction. We have found that conversion of the 4"-OH group to ether moieties decreases the immunogenic potential in mice relative to alpha-GalCer. Yet, the benzyl-modified glycolipids are able to produce a distinct pro-inflammatory immune response. The crystal structures suggest an extra hydrophobic interaction between the benzyl moiety and the alpha2-helix of CD1d.

4"-O-Alkylated alpha-Galactosylceramide Analogues as iNKT-Cell Antigens: Synthetic, Biological, and Structural Studies.,Janssens J, Bitra A, Wang J, Decruy T, Venken K, van der Eycken J, Elewaut D, Zajonc DM, van Calenbergh S ChemMedChem. 2019 Jan 8;14(1):147-168. doi: 10.1002/cmdc.201800649. Epub 2018 Dec, 17. PMID:30556652[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Janssens J, Bitra A, Wang J, Decruy T, Venken K, van der Eycken J, Elewaut D, Zajonc DM, van Calenbergh S. 4"-O-Alkylated alpha-Galactosylceramide Analogues as iNKT-Cell Antigens: Synthetic, Biological, and Structural Studies. ChemMedChem. 2019 Jan 8;14(1):147-168. doi: 10.1002/cmdc.201800649. Epub 2018 Dec, 17. PMID:30556652 doi:http://dx.doi.org/10.1002/cmdc.201800649

6mjq, resolution 3.00Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=6mjq&oldid=2989264"