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| | <StructureSection load='2bkt' size='340' side='right'caption='[[2bkt]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='2bkt' size='340' side='right'caption='[[2bkt]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bkt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BKT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BKT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bkt]] 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=2BKT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BKT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RPF:1-{4-[3-(2-METHOXY-BENZYLOXY)-PROPOXY]-PHENYL}-6-(1,2,,3,4-TETRAHYDRO-QUINOLIN-7-YLOXYMETHYL)-PIPERAZIN-2-ONE'>RPF</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]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1bbs|1bbs]], [[1bil|1bil]], [[1bim|1bim]], [[1hrn|1hrn]], [[1pr7|1pr7]], [[1pr8|1pr8]], [[1rne|1rne]], [[1uhq|1uhq]], [[2bks|2bks]], [[2ren|2ren]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RPF:1-{4-[3-(2-METHOXY-BENZYLOXY)-PROPOXY]-PHENYL}-6-(1,2,,3,4-TETRAHYDRO-QUINOLIN-7-YLOXYMETHYL)-PIPERAZIN-2-ONE'>RPF</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Renin Renin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.15 3.4.23.15] </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=2bkt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bkt OCA], [https://pdbe.org/2bkt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bkt RCSB], [https://www.ebi.ac.uk/pdbsum/2bkt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bkt 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=2bkt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bkt OCA], [https://pdbe.org/2bkt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bkt RCSB], [https://www.ebi.ac.uk/pdbsum/2bkt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bkt ProSAT]</span></td></tr> |
| | </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>
| + | [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.
| + | [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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Renin]]
| + | [[Category: Bryant JW]] |
| - | [[Category: Bryant, J W]] | + | [[Category: Clay EH]] |
| - | [[Category: Clay, E H]] | + | [[Category: Edmunds JJ]] |
| - | [[Category: Edmunds, J J]] | + | [[Category: Holsworth DD]] |
| - | [[Category: Holsworth, D D]] | + | [[Category: Jalaie M]] |
| - | [[Category: Jalaie, M]] | + | [[Category: Powell NA]] |
| - | [[Category: Powell, N A]] | + | [[Category: Ryan JM]] |
| - | [[Category: Ryan, J M]] | + | [[Category: Zhang E]] |
| - | [[Category: Zhang, E]] | + | |
| - | [[Category: Aspartyl protease]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Disease
RENI_HUMAN Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM: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).[1] Defects in REN are the cause of familial juvenile hyperuricemic nephropathy type 2 (HNFJ2) [MIM:613092. It is a renal disease characterized by juvenile onset of hyperuricemia, slowly progressive renal failure and anemia.[2]
Function
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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
We have found that both enantiomeric configurations of the 6-alkoxymethyl-1-aryl-2-piperazinone scaffold display equipotent renin inhibition activity and similar SAR patterns. This enantiomeric flexibility is in contrast to a previously reported 3-alkoxymethyl-4-arylpiperidine scaffold.
Equipotent activity in both enantiomers of a series of ketopiperazine-based renin inhibitors.,Powell NA, Clay EH, Holsworth DD, Bryant JW, Ryan MJ, Jalaie M, Zhang E, Edmunds JJ Bioorg Med Chem Lett. 2005 May 2;15(9):2371-4. PMID:15837327[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gribouval O, Gonzales M, Neuhaus T, Aziza J, Bieth E, Laurent N, Bouton JM, Feuillet F, Makni S, Ben Amar H, Laube G, Delezoide AL, Bouvier R, Dijoud F, Ollagnon-Roman E, Roume J, Joubert M, Antignac C, Gubler MC. Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet. 2005 Sep;37(9):964-8. Epub 2005 Aug 14. PMID:16116425 doi:ng1623
- ↑ Zivna M, Hulkova H, Matignon M, Hodanova K, Vylet'al P, Kalbacova M, Baresova V, Sikora J, Blazkova H, Zivny J, Ivanek R, Stranecky V, Sovova J, Claes K, Lerut E, Fryns JP, Hart PS, Hart TC, Adams JN, Pawtowski A, Clemessy M, Gasc JM, Gubler MC, Antignac C, Elleder M, Kapp K, Grimbert P, Bleyer AJ, Kmoch S. Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure. Am J Hum Genet. 2009 Aug;85(2):204-13. Epub 2009 Aug 6. PMID:19664745 doi:10.1016/j.ajhg.2009.07.010
- ↑ Powell NA, Clay EH, Holsworth DD, Bryant JW, Ryan MJ, Jalaie M, Zhang E, Edmunds JJ. Equipotent activity in both enantiomers of a series of ketopiperazine-based renin inhibitors. Bioorg Med Chem Lett. 2005 May 2;15(9):2371-4. PMID:15837327 doi:10.1016/j.bmcl.2005.02.085
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