View source for 7xwa


==Crystal structure of the receptor binding domain of SARS-CoV-2 Omicron BA.4/5 variant spike protein in complex with its receptor ACE2==
<StructureSection load='7xwa' size='340' side='right'caption='[[7xwa]], [[Resolution|resolution]] 3.36&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7xwa]] 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=7XWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XWA 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]] 3.36&#8491;</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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <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=7xwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xwa OCA], [https://pdbe.org/7xwa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xwa RCSB], [https://www.ebi.ac.uk/pdbsum/7xwa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xwa 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 ==
After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2.

Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5.,Kimura I, Yamasoba D, Tamura T, Nao N, Suzuki T, Oda Y, Mitoma S, Ito J, Nasser H, Zahradnik J, Uriu K, Fujita S, Kosugi Y, Wang L, Tsuda M, Kishimoto M, Ito H, Suzuki R, Shimizu R, Begum MM, Yoshimatsu K, Kimura KT, Sasaki J, Sasaki-Tabata K, Yamamoto Y, Nagamoto T, Kanamune J, Kobiyama K, Asakura H, Nagashima M, Sadamasu K, Yoshimura K, Shirakawa K, Takaori-Kondo A, Kuramochi J, Schreiber G, Ishii KJ, Hashiguchi T, Ikeda T, Saito A, Fukuhara T, Tanaka S, Matsuno K, Sato K Cell. 2022 Oct 13;185(21):3992-4007.e16. doi: 10.1016/j.cell.2022.09.018. Epub , 2022 Sep 14. PMID:36198317<ref>PMID:36198317</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7xwa" style="background-color:#fffaf0;"></div>

==See Also==
*[[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: Hashiguchi T]]
[[Category: Kimura K]]
[[Category: Suzuki T]]