3sci: Difference between revisions

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-[[Image:3sci.jpg|left|200px]]
-<!--
+==Crystal structure of spike protein receptor-binding domain from a predicted SARS coronavirus human strain complexed with human receptor ACE2==
-The line below this paragraph, containing "STRUCTURE_3sci", creates the "Structure Box" on the page.
+<StructureSection load='3sci' size='340' side='right'caption='[[3sci]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3sci]] 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-related_coronavirus Severe acute respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SCI FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_3sci|  PDB=3sci  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3sci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sci OCA], [https://pdbe.org/3sci PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sci RCSB], [https://www.ebi.ac.uk/pdbsum/3sci PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sci 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 severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional, and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals.
-===Crystal structure of spike protein receptor-binding domain from a predicted SARS coronavirus human strain complexed with human receptor ACE2===
+Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus.,Wu K, Peng G, Wilken M, Geraghty RJ, Li F J Biol Chem. 2012 Mar 16;287(12):8904-11. Epub 2012 Jan 30. PMID:22291007<ref>PMID:22291007</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3sci" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-[[3sci]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SCI OCA].
+*[[Angiotensin-Converting Enzyme 3D structures|Angiotensin-Converting Enzyme 3D structures]]
-[[Category: Angiotensin-converting enzyme 2]]
+*[[Sandbox 3001|Sandbox 3001]]
+*[[Spike protein 3D structures|Spike protein 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Sars coronavirus]]
+[[Category: Large Structures]]
-[[Category: Geraghty, R.]]
+[[Category: Severe acute respiratory syndrome-related coronavirus]]
-[[Category: Li, F.]]
+[[Category: Geraghty R]]
-[[Category: Peng, G.]]
+[[Category: Li F]]
-[[Category: Wilken, M.]]
+[[Category: Peng G]]
-[[Category: Wu, K.]]
+[[Category: Wilken M]]
-[[Category: Beta sheet]]
+[[Category: Wu K]]
-[[Category: Hydrolase-viral protein complex]]