View source for 2x94


==Crystal structure of AnCE-perindoprilat complex==
<StructureSection load='2x94' size='340' side='right'caption='[[2x94]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2x94]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X94 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X94 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=X94:PERINDOPRILAT'>X94</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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;'>[[1j38|1j38]], [[1j36|1j36]], [[1j37|1j37]], [[2x8z|2x8z]], [[2x8y|2x8y]], [[2x91|2x91]], [[2x95|2x95]], [[2x92|2x92]], [[2x96|2x96]], [[2x97|2x97]], [[2x93|2x93]], [[2x90|2x90]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Peptidyl-dipeptidase_A Peptidyl-dipeptidase A], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.15.1 3.4.15.1] </span></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=2x94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x94 OCA], [https://pdbe.org/2x94 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x94 RCSB], [https://www.ebi.ac.uk/pdbsum/2x94 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x94 ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/ACE_DROME ACE_DROME]] May be involved in the specific maturation or degradation of a number of bioactive peptides. May play a role in the contractions of the heart, gut and testes, and in spermatid differentiation.<ref>PMID:12591244</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/x9/2x94_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2x94 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Angiotensin I-converting enzyme (ACE), one of the central components of the renin-angiotensin system, is a key therapeutic target for the treatment of hypertension and cardiovascular disorders. Human somatic ACE (sACE) has two homologous domains (N and C). The N- and C-domain catalytic sites have different activities toward various substrates. Moreover, some of the undesirable side effects of the currently available and widely used ACE inhibitors may arise from their targeting both domains leading to defects in other pathways. In addition, structural studies have shown that although both these domains have much in common at the inhibitor binding site, there are significant differences and these are greater at the peptide binding sites than regions distal to the active site. As a model system, we have used an ACE homologue from Drosophila melanogaster (AnCE, a single domain protein with ACE activity) to study ACE inhibitor binding. In an extensive study, we present high-resolution structures for native AnCE and in complex with six known antihypertensive drugs, a novel C-domain sACE specific inhibitor, lisW-S, and two sACE domain-specific phosphinic peptidyl inhibitors, RXPA380 and RXP407 (i.e., nine structures). These structures show detailed binding features of the inhibitors and highlight subtle changes in the orientation of side chains at different binding pockets in the active site in comparison with the active site of N- and C-domains of sACE. This study provides information about the structure-activity relationships that could be utilized for designing new inhibitors with improved domain selectivity for sACE.

High-resolution crystal structures of Drosophila melanogaster angiotensin-converting enzyme in complex with novel inhibitors and antihypertensive drugs.,Akif M, Georgiadis D, Mahajan A, Dive V, Sturrock ED, Isaac RE, Acharya KR J Mol Biol. 2010 Jul 16;400(3):502-17. Epub 2010 May 19. PMID:20488190<ref>PMID:20488190</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2x94" style="background-color:#fffaf0;"></div>

==See Also==
*[[Angiotensin-Converting Enzyme 3D structures|Angiotensin-Converting Enzyme 3D structures]]
*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drome]]
[[Category: Large Structures]]
[[Category: Peptidyl-dipeptidase A]]
[[Category: Acharya, K R]]
[[Category: Akif, M]]
[[Category: Dive, V]]
[[Category: Georgiadis, D]]
[[Category: Isaac, R E]]
[[Category: Mahajan, A]]
[[Category: Sturrock, E D]]
[[Category: Ace inhibitor]]
[[Category: Carboxypeptidase]]
[[Category: Glycoprotein]]
[[Category: Hydrolase]]
[[Category: Metalloprotease]]