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| | <StructureSection load='1r4l' size='340' side='right'caption='[[1r4l]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='1r4l' size='340' side='right'caption='[[1r4l]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1r4l]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R4L OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1R4L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1r4l]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R4L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R4L FirstGlance]. <br> |
| - | </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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=XX5:(S,S)-2-{1-CARBOXY-2-[3-(3,5-DICHLORO-BENZYL)-3H-IMIDAZOL-4-YL]-ETHYLAMINO}-4-METHYL-PENTANOIC+ACID'>XX5</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=XX5:(S,S)-2-{1-CARBOXY-2-[3-(3,5-DICHLORO-BENZYL)-3H-IMIDAZOL-4-YL]-ETHYLAMINO}-4-METHYL-PENTANOIC+ACID'>XX5</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1r42|1r42]]</div></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=1r4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r4l OCA], [https://pdbe.org/1r4l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r4l RCSB], [https://www.ebi.ac.uk/pdbsum/1r4l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r4l ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1r4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r4l OCA], [http://pdbe.org/1r4l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1r4l RCSB], [http://www.ebi.ac.uk/pdbsum/1r4l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1r4l ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dales, N A]] | + | [[Category: Dales NA]] |
| - | [[Category: Fisher, M]] | + | [[Category: Fisher M]] |
| - | [[Category: Menon, S]] | + | [[Category: Menon S]] |
| - | [[Category: Pantoliano, M W]] | + | [[Category: Pantoliano MW]] |
| - | [[Category: Parsons, T]] | + | [[Category: Parsons T]] |
| - | [[Category: Patane, M A]] | + | [[Category: Patane MA]] |
| - | [[Category: Prasad, S G]] | + | [[Category: Prasad SG]] |
| - | [[Category: Ryan, D]] | + | [[Category: Ryan D]] |
| - | [[Category: Staker, B]] | + | [[Category: Staker B]] |
| - | [[Category: Tang, J]] | + | [[Category: Tang J]] |
| - | [[Category: Towler, P]] | + | [[Category: Towler P]] |
| - | [[Category: Williams, D]] | + | [[Category: Williams D]] |
| - | [[Category: Chloride ion binding site]]
| + | |
| - | [[Category: Collectrin homology domain]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Inhibitor bound conformation]]
| + | |
| - | [[Category: Zinc ion binding site]]
| + | |
| - | [[Category: Zinc metallopeptidase domain]]
| + | |
| Structural highlights
Function
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.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The angiotensin-converting enzyme (ACE)-related carboxypeptidase, ACE2, is a type I integral membrane protein of 805 amino acids that contains one HEXXH + E zinc-binding consensus sequence. ACE2 has been implicated in the regulation of heart function and also as a functional receptor for the coronavirus that causes the severe acute respiratory syndrome (SARS). To gain further insights into this enzyme, the first crystal structures of the native and inhibitor-bound forms of the ACE2 extracellular domains were solved to 2.2- and 3.0-A resolution, respectively. Comparison of these structures revealed a large inhibitor-dependent hinge-bending movement of one catalytic subdomain relative to the other ( approximately 16 degrees ) that brings important residues into position for catalysis. The potent inhibitor MLN-4760 ((S,S)-2-[1-carboxy-2-[3-(3,5-dichlorobenzyl)-3H-imidazol4-yl]-ethylamino] -4-methylpentanoic acid) makes key binding interactions within the active site and offers insights regarding the action of residues involved in catalysis and substrate specificity. A few active site residue substitutions in ACE2 relative to ACE appear to eliminate the S(2)' substrate-binding subsite and account for the observed reactivity change from the peptidyl dipeptidase activity of ACE to the carboxypeptidase activity of ACE2.
ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis.,Towler P, Staker B, Prasad SG, Menon S, Tang J, Parsons T, Ryan D, Fisher M, Williams D, Dales NA, Patane MA, Pantoliano MW J Biol Chem. 2004 Apr 23;279(17):17996-8007. Epub 2004 Jan 30. PMID:14754895[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000 Sep 1;87(5):E1-9. PMID:10969042
- ↑ Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000 Oct 27;275(43):33238-43. PMID:10924499 doi:http://dx.doi.org/10.1074/jbc.M002615200
- ↑ Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003 Nov 27;426(6965):450-4. PMID:14647384 doi:http://dx.doi.org/10.1038/nature02145
- ↑ Towler P, Staker B, Prasad SG, Menon S, Tang J, Parsons T, Ryan D, Fisher M, Williams D, Dales NA, Patane MA, Pantoliano MW. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J Biol Chem. 2004 Apr 23;279(17):17996-8007. Epub 2004 Jan 30. PMID:14754895 doi:10.1074/jbc.M311191200
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