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| | ==Crystal structure of human aminopeptidase A complexed with aspartate and calcium== | | ==Crystal structure of human aminopeptidase A complexed with aspartate and calcium== |
| - | <StructureSection load='4kxa' size='340' side='right' caption='[[4kxa]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='4kxa' size='340' side='right'caption='[[4kxa]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kxa]] is a 1 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=4KXA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KXA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4kxa]] is a 1 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=4KXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KXA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ASP:ASPARTIC+ACID'>ASP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kx7|4kx7]], [[4kx8|4kx8]], [[4kx9|4kx9]], [[4kxb|4kxb]], [[4kxc|4kxc]], [[4kxd|4kxd]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASP:ASPARTIC+ACID'>ASP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900017:triacetyl-beta-chitotriose'>PRD_900017</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <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 HUMAN])</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=4kxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kxa OCA], [https://pdbe.org/4kxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kxa RCSB], [https://www.ebi.ac.uk/pdbsum/4kxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kxa ProSAT]</span></td></tr> |
| - | <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>
| + | |
| - | <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=4kxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kxa OCA], [http://pdbe.org/4kxa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kxa RCSB], [http://www.ebi.ac.uk/pdbsum/4kxa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kxa ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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. | + | [https://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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Aminopeptidase|Aminopeptidase]] | + | *[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glutamyl aminopeptidase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, F]] | + | [[Category: Li F]] |
| - | [[Category: Lin, Y Y]] | + | [[Category: Lin YY]] |
| - | [[Category: Liu, C]] | + | [[Category: Liu C]] |
| - | [[Category: Yang, Y]] | + | [[Category: Yang Y]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Zinc-aminopeptidase]]
| + | |
| Structural highlights
4kxa is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.4Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yang Y, Liu C, Lin YL, Li F. Structural insights into central hypertension regulation by human aminopeptidase a. J Biol Chem. 2013 Aug 30;288(35):25638-45. doi: 10.1074/jbc.M113.494955. Epub, 2013 Jul 25. PMID:23888046 doi:10.1074/jbc.M113.494955
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