7bh9: Difference between revisions

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-'''Unreleased structure'''
-The entry 7bh9 is ON HOLD
+==SARS-CoV-2 RBD-62 in complex with ACE2 peptidase domain==
+<StructureSection load='7bh9' size='340' side='right'caption='[[7bh9]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7bh9]] is a 2 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=7BH9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BH9 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]] 2.9&#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=7bh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bh9 OCA], [https://pdbe.org/7bh9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bh9 RCSB], [https://www.ebi.ac.uk/pdbsum/7bh9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bh9 ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+SARS-CoV-2 variants of interest and concern will continue to emerge for the duration of the COVID-19 pandemic. To map mutations in the receptor-binding domain (RBD) of the spike protein that affect binding to angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, we applied in vitro evolution to affinity-mature the RBD. Multiple rounds of random mutagenic libraries of the RBD were sorted against decreasing concentrations of ACE2, resulting in the selection of higher affinity RBD binders. We found that mutations present in more transmissible viruses (S477N, E484K and N501Y) were preferentially selected in our high-throughput screen. Evolved RBD mutants include prominently the amino acid substitutions found in the RBDs of B.1.620, B.1.1.7 (Alpha), B1.351 (Beta) and P.1 (Gamma) variants. Moreover, the incidence of RBD mutations in the population as presented in the GISAID database (April 2021) is positively correlated with increased binding affinity to ACE2. Further in vitro evolution increased binding by 1,000-fold and identified mutations that may be more infectious if they evolve in the circulating viral population, for example, Q498R is epistatic to N501Y. We show that our high-affinity variant RBD-62 can be used as a drug to inhibit infection with SARS-CoV-2 and variants Alpha, Beta and Gamma in vitro. In a model of SARS-CoV-2 challenge in hamster, RBD-62 significantly reduced clinical disease when administered before or after infection. A 2.9 A cryo-electron microscopy structure of the high-affinity complex of RBD-62 and ACE2, including all rapidly spreading mutations, provides a structural basis for future drug and vaccine development and for in silico evaluation of known antibodies.
-Authors: Elad, N., Dym, O., Zahradnik, J., Schreiber, G.
+SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution.,Zahradnik J, Marciano S, Shemesh M, Zoler E, Harari D, Chiaravalli J, Meyer B, Rudich Y, Li C, Marton I, Dym O, Elad N, Lewis MG, Andersen H, Gagne M, Seder RA, Douek DC, Schreiber G Nat Microbiol. 2021 Sep;6(9):1188-1198. doi: 10.1038/s41564-021-00954-4. Epub , 2021 Aug 16. PMID:34400835<ref>PMID:34400835</ref>
-Description: SARS-CoV-2 RBD-62 in complex with ACE2 peptidase domain
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Schreiber, G]]
+<div class="pdbe-citations 7bh9" style="background-color:#fffaf0;"></div>
-[[Category: Elad, N]]
-[[Category: Zahradnik, J]]
+==See Also==
-[[Category: Dym, O]]
+*[[Angiotensin-Converting Enzyme 3D structures|Angiotensin-Converting Enzyme 3D structures]]
+*[[Spike protein 3D structures|Spike protein 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Severe acute respiratory syndrome coronavirus 2]]
+[[Category: Dym O]]
+[[Category: Elad N]]
+[[Category: Schreiber G]]
+[[Category: Zahradnik J]]