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[[Image:2bks.gif|left|200px]]<br />
<applet load="2bks" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2bks, resolution 2.2&Aring;" />
'''CRYSTAL STRUCTURE OF RENIN-PF00074777 COMPLEX'''<br />


==Overview==
==crystal structure of Renin-PF00074777 complex==
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.
<StructureSection load='2bks' size='340' side='right'caption='[[2bks]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2bks]] 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=2BKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BKS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PZ1:(6R)-6-({[1-(3-HYDROXYPROPYL)-1,7-DIHYDROQUINOLIN-7-YL]OXY}METHYL)-1-(4-{3-[(2-METHOXYBENZYL)OXY]PROPOXY}PHENYL)PIPERAZIN-2-ONE'>PZ1</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=2bks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bks OCA], [https://pdbe.org/2bks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bks RCSB], [https://www.ebi.ac.uk/pdbsum/2bks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bks ProSAT]</span></td></tr>
</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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bk/2bks_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2bks ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


==About this Structure==
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<ref>PMID:15837327</ref>
2BKS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PZ1 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BKS OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15837327 15837327]
</div>
<div class="pdbe-citations 2bks" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Renin|Renin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Renin]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[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: PZ1]]
[[Category: aspartic proteinase]]
[[Category: aspartyl protease]]
[[Category: glycoprotein]]
[[Category: hydrolase]]
[[Category: plasma]]
[[Category: polymorphism]]
[[Category: signal]]
[[Category: zymogen]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov  5 17:41:44 2007''

Latest revision as of 12:01, 6 November 2024

crystal structure of Renin-PF00074777 complexcrystal structure of Renin-PF00074777 complex

Structural highlights

2bks is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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

2bks, resolution 2.20Å

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