7crf

From Proteopedia

(Difference between revisions)

Revision as of 16:14, 29 November 2023

Crystal structure of human TLR8 in complex with CU-CPD107

Structural highlights

7crf is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.89Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TLR8_HUMAN Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.^[1]

Publication Abstract from PubMed

Small-molecule modulators of TLR8 have drawn much interests as it plays pivotal roles in the innate immune response to single-stranded RNAs (ssRNAs) derived from viruses. However, their clinical uses are limited because they can invoke an uncontrolled, global inflammatory response. The efforts described herein culminate in the fortuitous discovery of a tetrasubstituted imidazole CU-CPD107 which inhibits R848-induced TLR8 signaling. In stark contrast, CU-CPD107 shows unexpected synergistic agonist activities in the presence of ssRNA, while CU-CPD107 alone is unable to influence TLR8 signaling. CU-CPD107's unique, dichotomous behavior sheds light on a way to approach TLR agonists. CU-CPD107 offers the opportunity to avoid the undesired, global inflammation side effects that have rendered imidazoquinolines clinically irrelevant, providing an insight for the development of antiviral drugs.

Tetrasubstituted imidazoles as incognito Toll-like receptor 8 a(nta)gonists.,Yang Y, Csakai A, Jiang S, Smith C, Tanji H, Huang J, Jones T, Sakaniwa K, Broadwell L, Shi C, Soti S, Ohto U, Fang Y, Shen S, Deng F, Shimizu T, Yin H Nat Commun. 2021 Jul 16;12(1):4351. doi: 10.1038/s41467-021-24536-4. PMID:34272380^[2]

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

References

↑ Doyle SL, Jefferies CA, Feighery C, O'Neill LA. Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase. J Biol Chem. 2007 Dec 21;282(51):36953-60. Epub 2007 Oct 11. PMID:17932028 doi:10.1074/jbc.M707682200
↑ Yang Y, Csakai A, Jiang S, Smith C, Tanji H, Huang J, Jones T, Sakaniwa K, Broadwell L, Shi C, Soti S, Ohto U, Fang Y, Shen S, Deng F, Shimizu T, Yin H. Tetrasubstituted imidazoles as incognito Toll-like receptor 8 a(nta)gonists. Nat Commun. 2021 Jul 16;12(1):4351. doi: 10.1038/s41467-021-24536-4. PMID:34272380 doi:http://dx.doi.org/10.1038/s41467-021-24536-4

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7crf"

@@ Line 3: / Line 3: @@
 <StructureSection load='7crf' size='340' side='right'caption='[[7crf]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7crf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CRF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CRF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7crf]] 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=7CRF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CRF FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GD0:1-[2-(ethoxymethyl)-4-iodanyl-5-phenyl-imidazol-1-yl]-2-methyl-propan-2-ol'>GD0</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.89&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TLR8, UNQ249/PRO286 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GD0:1-[2-(ethoxymethyl)-4-iodanyl-5-phenyl-imidazol-1-yl]-2-methyl-propan-2-ol'>GD0</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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'>[https://proteopedia.org/fgij/fg.htm?mol=7crf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7crf OCA], [https://pdbe.org/7crf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7crf RCSB], [https://www.ebi.ac.uk/pdbsum/7crf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7crf ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/TLR8_HUMAN TLR8_HUMAN]] Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.<ref>PMID:17932028</ref>
+[https://www.uniprot.org/uniprot/TLR8_HUMAN TLR8_HUMAN] Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.<ref>PMID:17932028</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 7crf" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ohto, U]]
+[[Category: Ohto U]]
-[[Category: Sakaniwa, K]]
+[[Category: Sakaniwa K]]
-[[Category: Shimizu, T]]
+[[Category: Shimizu T]]
-[[Category: Tanji, H]]
+[[Category: Tanji H]]
-[[Category: Immune system]]

7crf

From Proteopedia

Revision as of 16:14, 29 November 2023

Crystal structure of human TLR8 in complex with CU-CPD107

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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