View source for 8xsf


==SARS-CoV-2 RBD + IMCAS-364 + hACE2==
<StructureSection load='8xsf' size='340' side='right'caption='[[8xsf]], [[Resolution|resolution]] 2.16&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8xsf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8XSF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XSF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.16&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8xsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xsf OCA], [https://pdbe.org/8xsf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xsf RCSB], [https://www.ebi.ac.uk/pdbsum/8xsf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xsf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACE2_HUMAN ACE2_HUMAN] Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.<ref>PMID:10969042</ref> <ref>PMID:10924499</ref> <ref>PMID:14647384</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The game between therapeutic monoclonal antibodies (mAbs) and continuously emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has favored the virus, as most therapeutic mAbs have been evaded. Addressing this challenge, we systematically explored a reproducible bispecific antibody (bsAb)-dependent synergistic effect in this study. It could effectively restore the neutralizing activity of the bsAb when any of its single mAbs is escaped by variants. This synergy is primarily attributed to the binding angle of receptor-binding domain (RBD)-5, facilitating inter-spike cross-linking and promoting cryptic epitope exposure that classical antibody cocktails cannot achieve. Furthermore, RBD-5 with RBD-2, RBD-6, and RBD-7, alongside RBD-8, also exhibit significantly enhanced effects. This study not only shifts the paradigm in understanding antibody interactions but paves the way for developing more effective therapeutic antibodies against rapidly mutating SARS-CoV-2, with Dia-19 already showing promise against emerging variants like BA.2.86, EG.5.1, and JN.1.

Deciphering a reliable synergistic bispecific strategy of rescuing antibodies for SARS-CoV-2 escape variants, including BA.2.86, EG.5.1, and JN.1.,Tong Z, Tong J, Lei W, Xie Y, Cui Y, Jia G, Li S, Zhang Z, Cheng Z, Xing X, Ma H, Deng L, Zhang R, Zhao X, Liu K, Wang Q, Qi J, Huang H, Song R, Su Z, Wu G, Lou J, Gao GF Cell Rep. 2024 Jun 25;43(6):114338. doi: 10.1016/j.celrep.2024.114338. Epub 2024 , Jun 8. PMID:38850530<ref>PMID:38850530</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8xsf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Cui Y]]
[[Category: Gao GF]]
[[Category: Qi J]]
[[Category: Tong J]]
[[Category: Tong Z]]
[[Category: Xie Y]]