2fs4: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2fs4.gif|left|200px]]
- {{Structure
+==Ketopiperazine-Based Renin Inhibitors: Optimization of the C ring==
-|PDB= 2fs4 |SIZE=350|CAPTION= <scene name='initialview01'>2fs4</scene>, resolution 2.2&Aring;
+<StructureSection load='2fs4' size='340' side='right'caption='[[2fs4]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <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>
+<table><tr><td colspan='2'>[[2fs4]] 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=2FS4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FS4 FirstGlance]. <br>
-|ACTIVITY= [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]
+</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>
-|GENE= REN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+<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=2fs4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fs4 OCA], [https://pdbe.org/2fs4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fs4 RCSB], [https://www.ebi.ac.uk/pdbsum/2fs4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fs4 ProSAT]</span></td></tr>
+</table>
-'''Ketopiperazine-Based Renin Inhibitors: Optimization of the C ring'''
+== 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 ==
-==Overview==
+[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/fs/2fs4_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=2fs4 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
 A systematic investigation of the S3 sub-pocket activity requirements was conducted. It was observed that linear and sterically small side chain substituents are preferred in the S3 sub-pocket for optimal renin inhibition. Polar groups in the S3-sub-pocket were not well tolerated and caused a reduction in renin inhibitory activity. Further, compounds with clog P's &lt; or = 3 demonstrated a dramatic reduction in CYP3A4 inhibitory activity.
-==Disease==
+Ketopiperazine-based renin inhibitors: optimization of the "C" ring.,Holsworth DD, Cai C, Cheng XM, Cody WL, Downing DM, Erasga N, Lee C, Powell NA, Edmunds JJ, Stier M, Jalaie M, Zhang E, McConnell P, Ryan MJ, Bryant J, Li T, Kasani A, Hall E, Subedi R, Rahim M, Maiti S Bioorg Med Chem Lett. 2006 May 1;16(9):2500-4. Epub 2006 Feb 15. PMID:16480874<ref>PMID:16480874</ref>
-Known diseases associated with this structure: Hyperproreninemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=179820 179820]], Renal tubular dysgenesis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=179820 179820]]
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-FS4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FS4 OCA].
+</div>
+<div class="pdbe-citations 2fs4" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Ketopiperazine-based renin inhibitors: optimization of the "C" ring., Holsworth DD, Cai C, Cheng XM, Cody WL, Downing DM, Erasga N, Lee C, Powell NA, Edmunds JJ, Stier M, Jalaie M, Zhang E, McConnell P, Ryan MJ, Bryant J, Li T, Kasani A, Hall E, Subedi R, Rahim M, Maiti S, Bioorg Med Chem Lett. 2006 May 1;16(9):2500-4. Epub 2006 Feb 15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16480874 16480874]
+*[[Renin|Renin]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Renin]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Bryant J]]
-[[Category: Bryantb, J.]]
+[[Category: Cai C]]
-[[Category: C.]]
+[[Category: Cheng X-M]]
-[[Category: Caia, C.]]
+[[Category: Cody WL]]
-[[Category: Chenga, X M.]]
+[[Category: Downing DM]]
-[[Category: Codya, W L.]]
+[[Category: Edmunds JJ]]
-[[Category: Downinga, D M.]]
+[[Category: Erasga N]]
-[[Category: Edmundsa, J J.]]
+[[Category: Hall E]]
-[[Category: Erasgaa, N.]]
+[[Category: Holsworth DD]]
-[[Category: Hallc, E.]]
+[[Category: Jalaie M]]
-[[Category: Holsworth, D D.]]
+[[Category: Kasani A]]
-[[Category: Jalaiea, M.]]
+[[Category: Lee C]]
-[[Category: Kasanic, A.]]
+[[Category: Li T]]
-[[Category: Leea,]]
+[[Category: Maiti S]]
-[[Category: Lic, T.]]
+[[Category: McConnell P]]
-[[Category: Maitic, S.]]
+[[Category: Powell NA]]
-[[Category: McConnella, P.]]
+[[Category: Rahim M]]
-[[Category: Powella, N A.]]
+[[Category: Ryan MJ]]
-[[Category: Rahimc, M.]]
+[[Category: Stier M]]
-[[Category: Ryanb, M J.]]
+[[Category: Subedi R]]
-[[Category: Stiera, M.]]
+[[Category: Zhang E]]
-[[Category: Subedic, R.]]
-[[Category: Zhanga, E.]]
-[[Category: PZ1]]
-[[Category: protein-ligand complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:56:06 2008''