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5awd

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Revision as of 06:27, 31 May 2023

Crystal structure of human TLR8 in complex with N1-4-aminomethylbenzyl (IMDQ)

Structural highlights

5awd is a 1 chain structure with sequence from Homo sapiens. 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

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

Human Toll-like receptor 8 (hTLR8) is expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells. Engagement by TLR8 agonists evokes a distinct cytokine profile which favors the development of type 1 helper T cells. Crystal structures of the ectodomain of hTLR8 cocrystallized with two regioisomers of a dual TLR7/8-agonistic N1-substituted imidazoquinolines showed subtle differences in their interactions in the binding site of hTLR8. We hypothesized that the potency of a previously reported best-in-class pure TLR8 agonist, 3-pentylquinoline-2-amine, could be further enhanced by "designing in" functional groups that would mimic key intermolecular interactions that we had observed in the crystal structures. We performed a focused exploration of decorating the quinoline core with alkylamino groups at all possible positions. These studies have led to the identification of a novel TLR8 agonist that was approximately 20-fold more potent than the parent compound and displays prominent adjuvantic activity in a rabbit model of immunization.

Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity.,Beesu M, Caruso G, Salyer AC, Khetani KK, Sil D, Weerasinghe M, Tanji H, Ohto U, Shimizu T, David SA J Med Chem. 2015 Oct 8;58(19):7833-49. doi: 10.1021/acs.jmedchem.5b01087. Epub, 2015 Sep 22. PMID:26351878^[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
↑ Beesu M, Caruso G, Salyer AC, Khetani KK, Sil D, Weerasinghe M, Tanji H, Ohto U, Shimizu T, David SA. Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity. J Med Chem. 2015 Oct 8;58(19):7833-49. doi: 10.1021/acs.jmedchem.5b01087. Epub, 2015 Sep 22. PMID:26351878 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b01087

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/5awd"

Categories: Homo sapiens | Large Structures | Ohto U | Shimizu T | Tanji H

@@ Line 3: / Line 3: @@
 <StructureSection load='5awd' size='340' side='right'caption='[[5awd]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5awd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AWD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AWD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5awd]] is a 1 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=5AWD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AWD 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=IDQ:1-[[4-(AMINOMETHYL)PHENYL]METHYL]-2-BUTYL-IMIDAZO[4,5-C]QUINOLIN-4-AMINE'>IDQ</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</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=IDQ:1-[[4-(AMINOMETHYL)PHENYL]METHYL]-2-BUTYL-IMIDAZO[4,5-C]QUINOLIN-4-AMINE'>IDQ</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5awa|5awa]], [[5awb|5awb]], [[5awc|5awc]]</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=5awd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5awd OCA], [https://pdbe.org/5awd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5awd RCSB], [https://www.ebi.ac.uk/pdbsum/5awd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5awd ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TLR8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5awd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5awd OCA], [http://pdbe.org/5awd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5awd RCSB], [http://www.ebi.ac.uk/pdbsum/5awd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5awd ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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 22: / Line 20: @@
 ==See Also==
-*[[Toll-like Receptors|Toll-like Receptors]]
+*[[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: Shimizu, T]]
+[[Category: Shimizu T]]
-[[Category: Tanji, H]]
+[[Category: Tanji H]]
-[[Category: Adjuvant]]
-[[Category: Glycosylation]]
-[[Category: Immune system]]
-[[Category: Linnate immunity]]
-[[Category: Tlr8]]
-[[Category: Vaccine adjuvant]]

5awd

From Proteopedia

Revision as of 06:27, 31 May 2023

Crystal structure of human TLR8 in complex with N1-4-aminomethylbenzyl (IMDQ)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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