2qpj

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[[Image:2qpj.jpg|left|200px]]
 
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{{Structure
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==Human NEP complexed with a bifunctional NEP/DPP IV inhibitor==
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|PDB= 2qpj |SIZE=350|CAPTION= <scene name='initialview01'>2qpj</scene>, resolution 2.05&Aring;
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<StructureSection load='2qpj' size='340' side='right'caption='[[2qpj]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <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>
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<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>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Neprilysin Neprilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.11 3.4.24.11]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
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|GENE= MME, EPN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<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>
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}}
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<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>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qp/2qpj_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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'''Human NEP complexed with a bifunctional NEP/DPP IV inhibitor'''
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2qpj" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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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.
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*[[Neprilysin|Neprilysin]]
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== References ==
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==About this Structure==
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<references/>
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2QPJ is a [[Single protein]] structure of 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=2QPJ OCA].
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__TOC__
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</StructureSection>
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/17704566 17704566]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Neprilysin]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Dale GE]]
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[[Category: Dale, G E.]]
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[[Category: Oefner C]]
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[[Category: Oefner, C.]]
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[[Category: I20]]
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[[Category: NAG]]
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[[Category: ZN]]
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[[Category: glycoprotein]]
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[[Category: hydrolase]]
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[[Category: lt3_9]]
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[[Category: membrane]]
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[[Category: metal-binding]]
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[[Category: signal-anchor]]
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[[Category: transmembrane]]
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[[Category: zinc-dependent metalloprotease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:28:10 2008''
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Current revision

Human NEP complexed with a bifunctional NEP/DPP IV inhibitor

PDB ID 2qpj

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