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<StructureSection load='6tt4' size='340' side='right'caption='[[6tt4]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='6tt4' size='340' side='right'caption='[[6tt4]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6tt4]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6tt4]] is a 2 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=6TT4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TT4 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=BO3:BORIC+ACID'>BO3</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FT8: | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=BO3:BORIC+ACID'>BO3</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FT8:(4~{S},7~{S},10~{a}~{S})-5-oxidanylidene-4-[[(2~{S})-3-phenyl-2-sulfanyl-propanoyl]amino]-2,3,4,7,8,9,10,10~{a}-octahydropyrido[2,1-b][1,3]thiazepine-7-carboxylic+acid'>FT8</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=XPE:3,6,9,12,15,18,21,24,27-NONAOXANONACOSANE-1,29-DIOL'>XPE</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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6tt4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tt4 OCA], [https://pdbe.org/6tt4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tt4 RCSB], [https://www.ebi.ac.uk/pdbsum/6tt4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tt4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 21: | Line 17: | ||
</div> | </div> | ||
<div class="pdbe-citations 6tt4" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6tt4" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Angiotensin-Converting Enzyme 3D structures|Angiotensin-Converting Enzyme 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Acharya | [[Category: Acharya KR]] | ||
[[Category: Cozier | [[Category: Cozier GE]] | ||
Latest revision as of 11:22, 17 October 2024
Crystal structure of 'Res_S2 mutant human Angiotensin-1 converting enzyme N-domain in complex with omapatrilat.Crystal structure of 'Res_S2 mutant human Angiotensin-1 converting enzyme N-domain in complex with omapatrilat.
Structural highlights
Publication Abstract from PubMedAngiotensin-converting enzyme (ACE) is best known for its formation of the vasopressor angiotensin II that controls blood pressure but is also involved in other physiological functions through the hydrolysis of a variety of peptide substrates. The enzyme contains two catalytic domains (nACE and cACE) that have different affinities for ACE substrates and inhibitors. We investigated whether nACE inhibitor backbones contain a unique property which allows them to take advantage of the hinging of nACE. Kinetic analysis showed that mutation of unique nACE residues in both the S2 pocket and around the prime subsites (S') to their C-domain counterparts each resulted in a decrease in affinity of nACE specific inhibitors (SG6, 33RE and ketoACE-13), but it required the combined S2_S' mutant to abrogate nACE-selectivity. However, this was not observed with the non-domain-selective inhibitors enalaprilat and omapatrilat. High resolution structures were determined for the minimally glycosylated nACE with the combined S2_S' mutations in complex with the ACE inhibitors 33RE (1.8 A), omapatrilat (1.8 A) and SG6 (1.7 A). These confirmed that the affinities of the nACE-selective SG6, 33RE and ketoACE-13 are not only affected by direct interactions with the immediate environment of the binding site, but also by more distal residues. This study provides evidence for a more general mechanism of ACE inhibition involving synergistic effects of not only the S2, S1' and S2' subsites, but also residues involved in the subdomain interface that effect the unique ways in which the two domains stabilise active site loops to favour inhibitor binding. ACE-domain selectivity extends beyond direct interacting residues at the active site.,Cozier GE, Lubbe L, Sturrock ED, Acharya KR Biochem J. 2020 Mar 20. pii: 222416. doi: 10.1042/BCJ20200060. PMID:32195541[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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