7rpv
From Proteopedia
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| - | ==== | + | ==Crystal structure of affinity-enhancing and catalytically inactive ACE2 in complex with SARS-CoV-2 RBD== |
| - | <StructureSection load='7rpv' size='340' side='right'caption='[[7rpv]]' scene=''> | + | <StructureSection load='7rpv' size='340' side='right'caption='[[7rpv]], [[Resolution|resolution]] 3.54Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7rpv]] is a 8 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=7RPV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RPV FirstGlance]. <br> |
| - | </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=7rpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rpv OCA], [https://pdbe.org/7rpv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rpv RCSB], [https://www.ebi.ac.uk/pdbsum/7rpv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rpv ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.54Å</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=7rpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rpv OCA], [https://pdbe.org/7rpv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rpv RCSB], [https://www.ebi.ac.uk/pdbsum/7rpv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rpv ProSAT]</span></td></tr> | ||
</table> | </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 == | ||
| + | Soluble Angiotensin-Converting Enzyme 2 (ACE2) constitutes an attractive antiviral capable of targeting a wide range of coronaviruses utilizing ACE2 as their receptor. Here, using structure-guided approaches, we developed divalent ACE2 molecules by grafting the extracellular ACE2-domain onto a human IgG1 or IgG3 (ACE2-Fc). These ACE2-Fcs harbor structurally validated mutations that enhance spike (S) binding and remove angiotensin enzymatic activity. The lead variant bound tightly to S, mediated in vitro neutralization of SARS-CoV-2 variants of concern (VOCs) with sub-nanomolar IC (50) and was capable of robust Fc-effector functions, including antibody-dependent-cellular cytotoxicity, phagocytosis and complement deposition. When tested in a stringent K18-hACE2 mouse model, it delayed death or effectively resolved lethal SARS-CoV-2 infection in a prophylactic or therapeutic setting utilizing the combined effect of neutralization and Fc-effector functions. These data confirm the utility of ACE2-Fcs as valuable agents in preventing and eliminating SARS-CoV-2 infection and demonstrate that ACE2-Fc therapeutic activity require Fc-effector functions. | ||
| + | |||
| + | Engineered ACE2-Fc counters murine lethal SARS-CoV-2 infection through direct neutralization and Fc-effector activities.,Chen Y, Sun L, Ullah I, Beaudoin-Bussieres G, Anand SP, Hederman AP, Tolbert WD, Sherburn R, Nguyen DN, Marchitto L, Ding S, Wu D, Luo Y, Gottumukkala S, Moran S, Kumar P, Piszczek G, Mothes W, Ackerman ME, Finzi A, Uchil PD, Gonzalez FJ, Pazgier M bioRxiv. 2021 Nov 24:2021.11.24.469776. doi: 10.1101/2021.11.24.469776. Preprint. PMID:34845451<ref>PMID:34845451</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7rpv" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Angiotensin-Converting Enzyme 3D structures|Angiotensin-Converting Enzyme 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Severe acute respiratory syndrome coronavirus 2]] |
| + | [[Category: Chen Y]] | ||
| + | [[Category: Pazgier M]] | ||
| + | [[Category: Tolbert DW]] | ||
Revision as of 16:35, 18 October 2023
Crystal structure of affinity-enhancing and catalytically inactive ACE2 in complex with SARS-CoV-2 RBD
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