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3g72

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{{Seed}}
 
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[[Image:3g72.jpg|left|200px]]
 
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==Design and Preparation of Potent, Non-Peptidic, Bioavailable Renin Inhibitors==
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The line below this paragraph, containing "STRUCTURE_3g72", creates the "Structure Box" on the page.
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<StructureSection load='3g72' size='340' side='right'caption='[[3g72]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3g72]] is a 2 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=3G72 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3G72 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A6T:(1S,5R)-7-{4-[3-(2-CHLORO-3,6-DIFLUOROPHENOXY)PROPYL]PHENYL}-N-CYCLOPROPYL-N-(2,3-DICHLOROBENZYL)-3,9-DIAZABICYCLO[3.3.1]NON-6-ENE-6-CARBOXAMIDE'>A6T</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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-->
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3g6z|3g6z]], [[3g70|3g70]]</td></tr>
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{{STRUCTURE_3g72| PDB=3g72 | SCENE= }}
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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/Renin Renin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.15 3.4.23.15] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3g72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g72 OCA], [http://pdbe.org/3g72 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3g72 RCSB], [http://www.ebi.ac.uk/pdbsum/3g72 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3g72 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN]] Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:[http://omim.org/entry/267430 267430]]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).<ref>PMID:16116425</ref> Defects in REN are the cause of familial juvenile hyperuricemic nephropathy type 2 (HNFJ2) [MIM:[http://omim.org/entry/613092 613092]]. It is a renal disease characterized by juvenile onset of hyperuricemia, slowly progressive renal failure and anemia.<ref>PMID:19664745</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN]] Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.
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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/g7/3g72_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3g72 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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Starting from known piperidine renin inhibitors, a new series of 3,9-diazabicyclo[3.3.1]nonene derivatives was rationally designed and prepared. Optimization of the positions 3, 6, and 7 of the diazabicyclonene template led to potent renin inhibitors. The substituents attached at the positions 6 and 7 were essential for the binding affinity of these compounds for renin. The introduction of a substituent attached at the position 3 did not modify the binding affinity but allowed the modulation of the ADME properties. Our efforts led to the discovery of compound (+)-26g that inhibits renin with an IC(50) of 0.20 nM in buffer and 19 nM in plasma. The pharmacokinetics properties of this and other similar compounds are discussed. Compound (+)-26g is well absorbed in rats and efficacious at 10 mg/kg in vivo.
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===Design and Preparation of Potent, Non-Peptidic, Bioavailable Renin Inhibitors===
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Design and preparation of potent, nonpeptidic, bioavailable renin inhibitors.,Bezencon O, Bur D, Weller T, Richard-Bildstein S, Remen L, Sifferlen T, Corminboeuf O, Grisostomi C, Boss C, Prade L, Delahaye S, Treiber A, Strickner P, Binkert C, Hess P, Steiner B, Fischli W J Med Chem. 2009 Jun 25;52(12):3689-702. PMID:19358611<ref>PMID:19358611</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 3g72" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19358611}}, adds the Publication Abstract to the page
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*[[Renin|Renin]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19358611 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19358611}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Human]]
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3G72 is a 2 chains structure of sequences 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=3G72 OCA].
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[[Category: Large Structures]]
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==Reference==
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<ref group="xtra">PMID:19358611</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
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[[Category: Renin]]
[[Category: Renin]]
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[[Category: Bezencon, O.]]
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[[Category: Bezencon, O]]
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[[Category: Boss, C.]]
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[[Category: Boss, C]]
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[[Category: Bur, D.]]
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[[Category: Bur, D]]
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[[Category: Fischli, W.]]
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[[Category: Fischli, W]]
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[[Category: Prade, L.]]
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[[Category: Prade, L]]
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[[Category: Weller, T.]]
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[[Category: Weller, T]]
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[[Category: Alternative splicing]]
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[[Category: Aspartyl protease]]
[[Category: Aspartyl protease]]
[[Category: Cleavage on pair of basic residue]]
[[Category: Cleavage on pair of basic residue]]
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[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Membrane]]
[[Category: Membrane]]
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[[Category: Polymorphism]]
 
[[Category: Protease]]
[[Category: Protease]]
[[Category: Renin human]]
[[Category: Renin human]]
[[Category: Secreted]]
[[Category: Secreted]]
[[Category: Zymogen]]
[[Category: Zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 1 09:15:34 2009''
 

Current revision

Design and Preparation of Potent, Non-Peptidic, Bioavailable Renin Inhibitors

PDB ID 3g72

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