1h70

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[[Image:1h70.jpg|left|200px]]<br /><applet load="1h70" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1h70, resolution 1.80&Aring;" />
 
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'''DDAH FROM PSEUDOMONAS AERUGINOSA. C249S MUTANT COMPLEXED WITH CITRULLINE'''<br />
 
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==Overview==
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==DDAH FROM PSEUDOMONAS AERUGINOSA. C249S MUTANT COMPLEXED WITH CITRULLINE==
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Nitric oxide synthase is inhibited by asymmetric NG-methylated derivatives of arginine whose cellular levels are controlled in part by dimethylarginine dimethylaminohydrolase (DDAH, EC 3.5.3.18). Levels of asymmetric NG,NG-dimethylarginine (ADMA) are known to correlate with certain disease states. Here, the first structure of a DDAH shows an unexpected similarity to arginine:glycine amidinotransferase (EC 2.1.4.1) and arginine deiminase (EC 3.5.3.6), thus defining a superfamily of arginine-modifying enzymes. The identification of a Cys-His-Glu catalytic triad and the structures of a Cys to Ser point mutant bound to both substrate and product suggest a reaction mechanism. Comparison of the ADMA-DDAH and arginine-amidinotransferase complexes reveals a dramatic rotation of the substrate that effectively maintains the orientation of the scissile bond of the substrate with respect to the catalytic residues. The DDAH structure will form a basis for the rational design of selective inhibitors, which are of potential use in modulating NO synthase activity in pathological settings.
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<StructureSection load='1h70' size='340' side='right'caption='[[1h70]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1h70]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H70 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H70 FirstGlance]. <br>
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1H70 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with <scene name='pdbligand=CIR:'>CIR</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Known structural/functional Site: <scene name='pdbsite=CIR:Cir+Binding+Site+For+Chain+A'>CIR</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H70 OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIR:CITRULLINE'>CIR</scene></td></tr>
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==Reference==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1h70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h70 OCA], [https://pdbe.org/1h70 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h70 RCSB], [https://www.ebi.ac.uk/pdbsum/1h70 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h70 ProSAT]</span></td></tr>
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Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase., Murray-Rust J, Leiper J, McAlister M, Phelan J, Tilley S, Santa Maria J, Vallance P, McDonald N, Nat Struct Biol. 2001 Aug;8(8):679-83. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11473257 11473257]
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</table>
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[[Category: Dimethylargininase]]
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== Function ==
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[https://www.uniprot.org/uniprot/DDAH_PSEAE DDAH_PSEAE] Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h7/1h70_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1h70 ConSurf].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Pseudomonas aeruginosa]]
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[[Category: Single protein]]
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[[Category: Leiper J]]
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[[Category: Leiper, J.]]
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[[Category: McAlister M]]
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[[Category: Mcalister, M.]]
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[[Category: McDonald N]]
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[[Category: Mcdonald, N.]]
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[[Category: Murray-Rust J]]
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[[Category: Murray-Rust, J.]]
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[[Category: Phelan J]]
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[[Category: Phelan, J.]]
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[[Category: Santamaria J]]
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[[Category: Santamaria, J.]]
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[[Category: Tilley S]]
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[[Category: Tilley, S.]]
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[[Category: Vallance P]]
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[[Category: Vallance, P.]]
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[[Category: CIR]]
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[[Category: ddah]]
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[[Category: hydrolase]]
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[[Category: nitric oxide synthase inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:58:07 2008''
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Current revision

DDAH FROM PSEUDOMONAS AERUGINOSA. C249S MUTANT COMPLEXED WITH CITRULLINE

PDB ID 1h70

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