4kx7

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{{STRUCTURE_4kx7| PDB=4kx7 | SCENE= }}
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==Crystal structure of human aminopeptidase A==
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===Crystal structure of human aminopeptidase A===
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<StructureSection load='4kx7' size='340' side='right' caption='[[4kx7]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23888046}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4kx7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KX7 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kx8|4kx8]], [[4kx9|4kx9]], [[4kxa|4kxa]], [[4kxb|4kxb]], [[4kxc|4kxc]], [[4kxd|4kxd]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ENPEP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutamyl_aminopeptidase Glutamyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.7 3.4.11.7] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4kx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kx7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kx7 RCSB], [http://www.ebi.ac.uk/pdbsum/4kx7 PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3' subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors.
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==Function==
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Structural insights into central hypertension regulation by human aminopeptidase a.,Yang Y, Liu C, Lin YL, Li F J Biol Chem. 2013 Aug 30;288(35):25638-45. doi: 10.1074/jbc.M113.494955. Epub, 2013 Jul 25. PMID:23888046<ref>PMID:23888046</ref>
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[[http://www.uniprot.org/uniprot/AMPE_HUMAN AMPE_HUMAN]] Appears to have a role in the catabolic pathway of the renin-angiotensin system. Probably plays a role in regulating growth and differentiation of early B-lineage cells.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4kx7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KX7 OCA].
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</div>
==See Also==
==See Also==
*[[Aminopeptidase|Aminopeptidase]]
*[[Aminopeptidase|Aminopeptidase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:023888046</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Glutamyl aminopeptidase]]
[[Category: Glutamyl aminopeptidase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Li, F.]]
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[[Category: Li, F]]
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[[Category: Lin, Y Y.]]
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[[Category: Lin, Y Y]]
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[[Category: Liu, C.]]
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[[Category: Liu, C]]
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[[Category: Yang, Y.]]
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[[Category: Yang, Y]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Zinc-aminopeptidase fold]]
[[Category: Zinc-aminopeptidase fold]]

Revision as of 15:22, 21 December 2014

Crystal structure of human aminopeptidase A

4kx7, resolution 2.15Å

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