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2qpj
From Proteopedia
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| - | {{STRUCTURE_2qpj| PDB=2qpj | SCENE= }} | ||
| - | ===Human NEP complexed with a bifunctional NEP/DPP IV inhibitor=== | ||
| - | {{ABSTRACT_PUBMED_17704566}} | ||
| - | == | + | ==Human NEP complexed with a bifunctional NEP/DPP IV inhibitor== |
| - | [[2qpj]] is a 1 chain structure with sequence from [ | + | <StructureSection load='2qpj' size='340' side='right'caption='[[2qpj]], [[Resolution|resolution]] 2.05Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2qpj]] 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=2QPJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QPJ 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]] 2.05Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I20:(2S)-2-({(2S)-3-[(R)-[(1R)-1-({(4S)-4-AMINO-5-[(2S)-2-CYANOPYRROLIDIN-1-YL]-5-OXOPENTANOYL}AMINO)ETHYL](HYDROXY)PHOSPHORYL]-2-BENZYLPROPANOYL}AMINO)PROPANOIC+ACID'>I20</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=2qpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qpj OCA], [https://pdbe.org/2qpj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qpj RCSB], [https://www.ebi.ac.uk/pdbsum/2qpj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qpj ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NEP_HUMAN NEP_HUMAN] Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9. Involved in the degradation of atrial natriuretic factor (ANF). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers.<ref>PMID:2531377</ref> <ref>PMID:15283675</ref> <ref>PMID:20876573</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/qp/2qpj_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=2qpj ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Neutral endopeptidase (NEP) is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor, as well as the incretin hormone glucagon-like peptide 1 (GLP-1), which is a potent stimulator of insulin secretion. The activity of GLP-1 is also rapidly abolished by the serine protease dipeptidyl peptidase IV (DPP-IV), which led to an elevated interest in inhibitors of this enzyme for the treatment of type II diabetes. A dual NEP/DPP-IV inhibitor concept is proposed, offering an alternative strategy for the treatment of type 2 diabetes. Here, the synthesis and crystal structures of the soluble extracellular domain of human NEP (residues 52-749) complexed with the NEP, competitive and potent dual NEP/DPP-IV inhibitor MCB3937 are described. | ||
| + | |||
| + | Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV.,Oefner C, Pierau S, Schulz H, Dale GE Acta Crystallogr D Biol Crystallogr. 2007 Sep;63(Pt 9):975-81. Epub 2007, Aug 17. PMID:17704566<ref>PMID:17704566</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2qpj" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Neprilysin|Neprilysin]] | *[[Neprilysin|Neprilysin]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Dale | + | [[Category: Dale GE]] |
| - | [[Category: Oefner | + | [[Category: Oefner C]] |
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Current revision
Human NEP complexed with a bifunctional NEP/DPP IV inhibitor
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