2jai: Difference between revisions

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-[[Image:2jai.jpg|left|200px]]
- {{Structure
+==DDAH1 complexed with citrulline==
-|PDB= 2jai |SIZE=350|CAPTION= <scene name='initialview01'>2jai</scene>, resolution 2.30&Aring;
+<StructureSection load='2jai' size='340' side='right'caption='[[2jai]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-|SITE= <scene name='pdbsite=AC1:Cir+Binding+Site+For+Chain+A'>AC1</scene>
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=CIR:CITRULLINE'>CIR</scene>
+<table><tr><td colspan='2'>[[2jai]] 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=2JAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JAI FirstGlance]. <br>
-|ACTIVITY= [http://en.wikipedia.org/wiki/Dimethylargininase Dimethylargininase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.18 3.5.3.18]
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
-|GENE=
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIR:CITRULLINE'>CIR</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=2jai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jai OCA], [https://pdbe.org/2jai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jai RCSB], [https://www.ebi.ac.uk/pdbsum/2jai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jai ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DDAH1_HUMAN DDAH1_HUMAN] Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.
+== 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/ja/2jai_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=2jai ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA) are endogenously produced amino acids that inhibit all three isoforms of nitric oxide synthase (NOS). ADMA accumulates in various disease states, including renal failure, diabetes and pulmonary hypertension, and its concentration in plasma is strongly predictive of premature cardiovascular disease and death. Both L-NMMA and ADMA are eliminated largely through active metabolism by dimethylarginine dimethylaminohydrolase (DDAH) and thus DDAH dysfunction may be a crucial unifying feature of increased cardiovascular risk. However, despite considerable interest in this pathway and in the role of ADMA as a cardiovascular risk factor, there is little evidence to support a causal role of ADMA in pathophysiology. Here we reveal the structure of human DDAH-1 and probe the function of DDAH-1 both by deleting the DDAH1 gene in mice and by using DDAH-specific inhibitors which, as we demonstrate by crystallography, bind to the active site of human DDAH-1. We show that loss of DDAH-1 activity leads to accumulation of ADMA and reduction in NO signaling. This in turn causes vascular pathophysiology, including endothelial dysfunction, increased systemic vascular resistance and elevated systemic and pulmonary blood pressure. Our results also suggest that DDAH inhibition could be harnessed therapeutically to reduce the vascular collapse associated with sepsis.
-'''DDAH1 COMPLEXED WITH CITRULLINE'''
+Disruption of methylarginine metabolism impairs vascular homeostasis.,Leiper J, Nandi M, Torondel B, Murray-Rust J, Malaki M, O'Hara B, Rossiter S, Anthony S, Madhani M, Selwood D, Smith C, Wojciak-Stothard B, Rudiger A, Stidwill R, McDonald NQ, Vallance P Nat Med. 2007 Feb;13(2):198-203. Epub 2007 Feb 4. PMID:17273169<ref>PMID:17273169</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-==About this Structure==
+</div>
-JAI 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=2JAI OCA].
+<div class="pdbe-citations 2jai" style="background-color:#fffaf0;"></div>
-[[Category: Dimethylargininase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Hara, B P.O.]]
+[[Category: Leiper JM]]
-[[Category: Leiper, J M.]]
+[[Category: McDonald NQ]]
-[[Category: Mcdonald, N Q.]]
+[[Category: Murray-Rust J]]
-[[Category: Murray-Rust, J.]]
+[[Category: O'Hara BP]]
-[[Category: Rossiter, S.]]
+[[Category: Rossiter S]]
-[[Category: Vallance, P.]]
+[[Category: Vallance P]]
-[[Category: CIR]]
-[[Category: ddah]]
-[[Category: hydrolase]]
-[[Category: nitric oxide synthase inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:39:23 2008''