7xgo
From Proteopedia
(Difference between revisions)
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==Human renin in complex with compound2== | ==Human renin in complex with compound2== | ||
| - | <StructureSection load='7xgo' size='340' side='right'caption='[[7xgo]]' scene=''> | + | <StructureSection load='7xgo' size='340' side='right'caption='[[7xgo]], [[Resolution|resolution]] 2.10Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XGO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7xgo]] 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=7XGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XGO FirstGlance]. <br> |
| - | </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=7xgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xgo OCA], [https://pdbe.org/7xgo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xgo RCSB], [https://www.ebi.ac.uk/pdbsum/7xgo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xgo ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</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=7xgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xgo OCA], [https://pdbe.org/7xgo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xgo RCSB], [https://www.ebi.ac.uk/pdbsum/7xgo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xgo ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == 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 == | ||
| + | [[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 == | ||
| + | The renin-angiotensin-aldosterone system (RAAS) plays a key role in the regulation of blood pressure. Renin, the first and rate-limiting enzyme of the RAAS, is an attractive target for the treatment of hypertension and cardiovascular/renal diseases. Therefore, various direct renin inhibitors (DRIs) have been researched over recent decades; however, most exhibited poor pharmacokinetics and oral bioavailability due to the peptidomimetic or nonpeptidomimetic structures with a molecular weight (MW) of >600, and only aliskiren is approved. This study introduces a novel class of DRIs comprised of a 2-carbamoyl morpholine scaffold. These compounds have a nonpeptidomimetic structure and a MW of <500. The representative compound 26 was highly potent despite not occupying S1'-S2' sites or the opened flap region used by other DRIs and exerted a significant antihypertensive efficacy via oral administration on double transgenic mice carrying both the human angiotensinogen and the human renin genes. | ||
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| + | Discovery of Novel 2-Carbamoyl Morpholine Derivatives as Highly Potent and Orally Active Direct Renin Inhibitors.,Iijima D, Sugama H, Awai N, Takahashi Y, Togashi Y, Takebe T, Xie J, Shen J, Ke Y, Akatsuka H, Kawaguchi T, Takedomi K, Kashima A, Nishio M, Inui Y, Yoneda H, Xia G, Iijima T ACS Med Chem Lett. 2022 Aug 1;13(8):1351-1357. doi:, 10.1021/acsmedchemlett.2c00280. eCollection 2022 Aug 11. PMID:35978678<ref>PMID:35978678</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7xgo" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Kashima A]] | [[Category: Kashima A]] | ||
Current revision
Human renin in complex with compound2
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