View source for 5lds


==Structure of the porcine aminopeptidase N ectodomain==
<StructureSection load='5lds' size='340' side='right'caption='[[5lds]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5lds]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LDS FirstGlance]. <br>
</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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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'>[https://proteopedia.org/fgij/fg.htm?mol=5lds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lds OCA], [https://pdbe.org/5lds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lds RCSB], [https://www.ebi.ac.uk/pdbsum/5lds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lds ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AMPN_PIG AMPN_PIG] Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May be involved in the metabolism of regulatory peptides of diverse cell types, responsible for the processing of peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines and involved the cleavage of peptides bound to major histocompatibility complex class II molecules of antigen presenting cells. May have a role in angiogenesis (By similarity). It is able to degrade Leu-enkephalin and Met-enkephalin but not cholecystokinin CCK8, neuromedin C (GRP-10), somatostatin-14, substance P and vasoactive intestinal peptide. In case of porcine transmissible gastroenteritis coronavirus (TGEV) and porcine respiratory coronavirus (PRCoV) infections, serves as a receptor for TGEV and PRCoV spike glycoprotein in a species-specific manner.<ref>PMID:7913510</ref> <ref>PMID:1350661</ref> <ref>PMID:7911642</ref> <ref>PMID:8985407</ref> <ref>PMID:9634079</ref> 
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== Publication Abstract from PubMed ==
Cell surface aminopeptidase N (APN) is a membrane-bound ectoenzyme that hydrolyzes proteins and peptides and regulates numerous cell functions. APN participates in tumor cell expansion and motility, and is a target for cancer therapies. Small drugs that bind to the APN active site inhibit catalysis and suppress tumor growth. APN is also a major cell entry receptor for coronavirus, which binds to a region distant from the active site. Three crystal structures that we determined of human and pig APN ectodomains defined the dynamic conformation of the protein. These structures offered snapshots of closed, intermediate and open APN, which represent distinct functional states. Coronavirus envelope proteins specifically recognized the open APN form, prevented ectodomain progression to the closed form and substrate hydrolysis. In addition, drugs that bind the active site inhibited both coronavirus binding to cell surface APN and infection; the drugs probably hindered APN transition to the virus-specific open form. We conclude that allosteric inhibition of APN functions occurs by ligand suppression of ectodomain motions necessary for catalysis and virus cell entry, as validated by locking APN with disulfides. Blocking APN dynamics can thus be a valuable approach to development of drugs that target this ectoenzyme.

Allosteric inhibition of aminopeptidase N functions related to tumor growth and virus infection.,Santiago C, Mudgal G, Reguera J, Recacha R, Albrecht S, Enjuanes L, Casasnovas JM Sci Rep. 2017 Apr 10;7:46045. doi: 10.1038/srep46045. PMID:28393915<ref>PMID:28393915</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5lds" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Casasnovas JM]]
[[Category: Mudgal G]]
[[Category: Reguera J]]
[[Category: Santiago C]]