View source for 8bn1


==The structures of Ace2 in complex with bicyclic peptide inhibitor==
<StructureSection load='8bn1' size='340' side='right'caption='[[8bn1]], [[Resolution|resolution]] 2.61&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8bn1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BN1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BN1 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]] 2.61&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4PH:4-METHYL-L-PHENYLALANINE'>4PH</scene>, <scene name='pdbligand=LFI:1-[3,5-bis(3-bromanylpropanoyl)-1,3,5-triazinan-1-yl]-3-bromanyl-propan-1-one'>LFI</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=8bn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bn1 OCA], [https://pdbe.org/8bn1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bn1 RCSB], [https://www.ebi.ac.uk/pdbsum/8bn1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bn1 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> 
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== Publication Abstract from PubMed ==
Angiotensin-converting enzyme 2 (ACE2) is a metalloprotease that cleaves angiotensin II, a peptide substrate involved in the regulation of hypertension. Here, we identified a series of constrained bicyclic peptides, Bicycle, inhibitors of human ACE2 by panning highly diverse bacteriophage display libraries. These were used to generate X-ray crystal structures which were used to inform the design of additional Bicycles with increased affinity and inhibition of ACE2 enzymatic activity. This novel structural class of ACE2 inhibitors is among the most potent ACE2 inhibitors yet described in vitro, representing a valuable tool to further probe ACE2 function and for potential therapeutic utility.

Structure-Guided Chemical Optimization of Bicyclic Peptide (Bicycle) Inhibitors of Angiotensin-Converting Enzyme 2.,Harman MAJ, Stanway SJ, Scott H, Demydchuk Y, Bezerra GA, Pellegrino S, Chen L, Brear P, Lulla A, Hyvonen M, Beswick PJ, Skynner MJ J Med Chem. 2023 Jul 27;66(14):9881-9893. doi: 10.1021/acs.jmedchem.3c00710. Epub , 2023 Jul 11. PMID:37433017<ref>PMID:37433017</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8bn1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Bezerra G]]
[[Category: Brear P]]
[[Category: Chen L]]
[[Category: Demydchuk Y]]
[[Category: Dods R]]
[[Category: Harman M]]
[[Category: Hyvonen M]]
[[Category: Lulla A]]
[[Category: Stanway S]]