7so0: Difference between revisions
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==Crystal Structure of the Engineered Tick Evasin EVA-P974(F31A) Complexed to Human Chemokine CCL2== | |||
<StructureSection load='7so0' size='340' side='right'caption='[[7so0]], [[Resolution|resolution]] 1.74Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7so0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Amblyomma_cajennense Amblyomma cajennense] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SO0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SO0 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]] 1.74Å</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=7so0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7so0 OCA], [https://pdbe.org/7so0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7so0 RCSB], [https://www.ebi.ac.uk/pdbsum/7so0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7so0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/EV974_AMBCJ EV974_AMBCJ] Salivary chemokine-binding protein which binds to host chemokines CCL1, CCL3, CCL4, CCL8, CCL17, CCL18 and CCL22.<ref>PMID:28655871</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
As natural chemokine inhibitors, evasin proteins produced in tick saliva are potential therapeutic agents for numerous inflammatory diseases. Engineering evasins to block the desired chemokines and avoid off-target side effects requires structural understanding of their target selectivity. Structures of the class A evasin EVA-P974 bound to human CC chemokine ligands 7 and 17 (CCL7 and CCL17) and to a CCL8-CCL7 chimera reveal that the specificity of class A evasins for chemokines of the CC subfamily is defined by conserved, rigid backbone-backbone interactions, whereas the preference for a subset of CC chemokines is controlled by side-chain interactions at four hotspots in flexible structural elements. Hotspot mutations alter target preference, enabling inhibition of selected chemokines. The structure of an engineered EVA-P974 bound to CCL2 reveals an underlying molecular mechanism of EVA-P974 target preference. These results provide a structure-based framework for engineering evasins as targeted antiinflammatory therapeutics. | |||
Structure-guided engineering of tick evasins for targeting chemokines in inflammatory diseases.,Bhusal RP, Aryal P, Devkota SR, Pokhrel R, Gunzburg MJ, Foster SR, Lim HD, Payne RJ, Wilce MCJ, Stone MJ Proc Natl Acad Sci U S A. 2022 Mar 1;119(9). pii: 2122105119. doi:, 10.1073/pnas.2122105119. PMID:35217625<ref>PMID:35217625</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7so0" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Devkota | ==See Also== | ||
[[Category: | *[[Monocyte chemoattractant protein|Monocyte chemoattractant protein]] | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Amblyomma cajennense]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Aryal P]] | |||
[[Category: Bhusal RP]] | |||
[[Category: Devkota SR]] | |||
[[Category: Stone MJ]] | |||
[[Category: Wilce MCJ]] | |||
Latest revision as of 19:53, 18 October 2023
Crystal Structure of the Engineered Tick Evasin EVA-P974(F31A) Complexed to Human Chemokine CCL2Crystal Structure of the Engineered Tick Evasin EVA-P974(F31A) Complexed to Human Chemokine CCL2
Structural highlights
FunctionEV974_AMBCJ Salivary chemokine-binding protein which binds to host chemokines CCL1, CCL3, CCL4, CCL8, CCL17, CCL18 and CCL22.[1] Publication Abstract from PubMedAs natural chemokine inhibitors, evasin proteins produced in tick saliva are potential therapeutic agents for numerous inflammatory diseases. Engineering evasins to block the desired chemokines and avoid off-target side effects requires structural understanding of their target selectivity. Structures of the class A evasin EVA-P974 bound to human CC chemokine ligands 7 and 17 (CCL7 and CCL17) and to a CCL8-CCL7 chimera reveal that the specificity of class A evasins for chemokines of the CC subfamily is defined by conserved, rigid backbone-backbone interactions, whereas the preference for a subset of CC chemokines is controlled by side-chain interactions at four hotspots in flexible structural elements. Hotspot mutations alter target preference, enabling inhibition of selected chemokines. The structure of an engineered EVA-P974 bound to CCL2 reveals an underlying molecular mechanism of EVA-P974 target preference. These results provide a structure-based framework for engineering evasins as targeted antiinflammatory therapeutics. Structure-guided engineering of tick evasins for targeting chemokines in inflammatory diseases.,Bhusal RP, Aryal P, Devkota SR, Pokhrel R, Gunzburg MJ, Foster SR, Lim HD, Payne RJ, Wilce MCJ, Stone MJ Proc Natl Acad Sci U S A. 2022 Mar 1;119(9). pii: 2122105119. doi:, 10.1073/pnas.2122105119. PMID:35217625[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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