4ryc
From Proteopedia
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==RENIN IN COMPLEXED WITH 4-methoxy-3-(3-methoxypropoxy)-N-{[(3S,4S)-4-{[(4-methylphenyl)sulfonyl]amino}pyrrolidin-3-yl]methyl}-N-(propan-2-yl)benzamide INHIBITOR== | ==RENIN IN COMPLEXED WITH 4-methoxy-3-(3-methoxypropoxy)-N-{[(3S,4S)-4-{[(4-methylphenyl)sulfonyl]amino}pyrrolidin-3-yl]methyl}-N-(propan-2-yl)benzamide INHIBITOR== | ||
| - | <StructureSection load='4ryc' size='340' side='right' caption='[[4ryc]], [[Resolution|resolution]] 2.45Å' scene=''> | + | <StructureSection load='4ryc' size='340' side='right'caption='[[4ryc]], [[Resolution|resolution]] 2.45Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4ryc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RYC OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[4ryc]] 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=4RYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RYC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3ZK:4-METHOXY-3-(3-METHOXYPROPOXY)-N-{[(3S,4S)-4-{[(4-METHYLPHENYL)SULFONYL]AMINO}PYRROLIDIN-3-YL]METHYL}-N-(PROPAN-2-YL)BENZAMIDE'>3ZK</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3ZK:4-METHOXY-3-(3-METHOXYPROPOXY)-N-{[(3S,4S)-4-{[(4-METHYLPHENYL)SULFONYL]AMINO}PYRROLIDIN-3-YL]METHYL}-N-(PROPAN-2-YL)BENZAMIDE'>3ZK</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4ryc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ryc OCA], [https://pdbe.org/4ryc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ryc RCSB], [https://www.ebi.ac.uk/pdbsum/4ryc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ryc ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN] Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:[https://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:[https://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> |
== 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. |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Recently, we reported on the discovery of (3S,4S)-disubstituted pyrrolidines (e.g., 2) as inhibitors of the human aspartyl protease renin. In our effort to further expand the scope of this novel class of direct renin inhibitors, a new sub-series was designed in which the prime site substituents are linked to the pyrrolidine core by a (3S)-amino functional group. In particular, analogs bearing the corresponding sulfonamide spacer (50, 51 and 54a) demonstrated a pronounced increase in in vitro potency compared to compound 2. | ||
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| + | trans-(3S,4S)-Disubstituted pyrrolidines as inhibitors of the human aspartyl protease renin. Part I: Prime site exploration using an amino linker.,Lorthiois E, Cumin F, Ehrhardt C, Kosaka T, Sellner H, Ostermann N, Francotte E, Wagner T, Maibaum J Bioorg Med Chem Lett. 2015 Apr 15;25(8):1782-6. doi: 10.1016/j.bmcl.2015.02.039. , Epub 2015 Feb 21. PMID:25782742<ref>PMID:25782742</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4ryc" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Renin|Renin]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Ostermann N]] |
| - | + | ||
Current revision
RENIN IN COMPLEXED WITH 4-methoxy-3-(3-methoxypropoxy)-N-{[(3S,4S)-4-{[(4-methylphenyl)sulfonyl]amino}pyrrolidin-3-yl]methyl}-N-(propan-2-yl)benzamide INHIBITOR
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