3q3t
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3q3t]] is a 2 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=3Q3T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q3T FirstGlance]. <br> | <table><tr><td colspan='2'>[[3q3t]] is a 2 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=3Q3T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q3T FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RX0:[(1S,3R,4S)-3-AMINO-4-HYDROXYCYCLOPENTYL]{(3R)-3-[(1S)-1-(BIPHENYL-2-YL)-1-HYDROXY-5-METHOXYPENTYL]PIPERIDIN-1-YL}METHANONE'>RX0</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]] 2.6Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RX0:[(1S,3R,4S)-3-AMINO-4-HYDROXYCYCLOPENTYL]{(3R)-3-[(1S)-1-(BIPHENYL-2-YL)-1-HYDROXY-5-METHOXYPENTYL]PIPERIDIN-1-YL}METHANONE'>RX0</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=3q3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q3t OCA], [https://pdbe.org/3q3t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q3t RCSB], [https://www.ebi.ac.uk/pdbsum/3q3t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q3t ProSAT]</span></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=3q3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q3t OCA], [https://pdbe.org/3q3t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q3t RCSB], [https://www.ebi.ac.uk/pdbsum/3q3t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q3t ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[https://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. | [https://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. | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension. | ||
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| - | Biphenyl/diphenyl ether renin inhibitors: Filling the S1 pocket of renin via the S3 pocket.,Yuan J, Simpson RD, Zhao W, Tice CM, Xu Z, Cacatian S, Jia L, Flaherty PT, Guo J, Ishchenko A, Wu Z, McKeever BM, Scott BB, Bukhtiyarov Y, Berbaum J, Panemangalore R, Bentley R, Doe CP, Harrison RK, McGeehan GM, Singh SB, Dillard LW, Baldwin JJ, Claremon DA Bioorg Med Chem Lett. 2011 Aug 15;21(16):4836-43. Epub 2011 Jun 17. PMID:21741239<ref>PMID:21741239</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 3q3t" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Revision as of 11:32, 14 March 2024
Alkyl Amine Renin Inhibitors: Filling S1 from S3
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