2e1w

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[[Image:2e1w.gif|left|200px]]<br /><applet load="2e1w" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2e1w, resolution 2.5&Aring;" />
 
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'''Crystal structure of adenosine deaminase complexed with potent inhibitors'''<br />
 
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==Overview==
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==Crystal structure of adenosine deaminase complexed with potent inhibitors==
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We disclose optimization efforts based on the novel non-nucleoside adenosine deaminase (ADA) inhibitor, 4 (K(i) = 680 nM). Structure-based drug design utilizing the crystal structure of the 4/ADA complex led to discovery of 5 (K(i) = 11 nM, BA = 30% in rats). Furthermore, from metabolic considerations, we discovered two inhibitors with improved oral bioavailability [6 (K(i) = 13 nM, BA = 44%) and 7 (K(i) = 9.8 nM, BA = 42%)]. 6 demonstrated in vivo efficacy in models of inflammation and lymphoma.
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<StructureSection load='2e1w' size='340' side='right'caption='[[2e1w]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2e1w]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1v78 1v78]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E1W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E1W FirstGlance]. <br>
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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]] 2.5&#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=FR6:1-{(1R,2S)-2-HYDROXY-1-[2-(1-NAPHTHYL)ETHYL]PROPYL}-1H-IMIDAZOLE-4-CARBOXAMIDE'>FR6</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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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=2e1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e1w OCA], [https://pdbe.org/2e1w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e1w RCSB], [https://www.ebi.ac.uk/pdbsum/2e1w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e1w ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ADA_BOVIN ADA_BOVIN] Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion (By similarity).
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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/e1/2e1w_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=2e1w ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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2E1W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=FR6:'>FR6</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1V78. Active as [http://en.wikipedia.org/wiki/Adenosine_deaminase Adenosine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.4 3.5.4.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E1W OCA].
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*[[Adenosine deaminase 3D structures|Adenosine deaminase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors., Terasaka T, Okumura H, Tsuji K, Kato T, Nakanishi I, Kinoshita T, Kato Y, Kuno M, Seki N, Naoe Y, Inoue T, Tanaka K, Nakamura K, J Med Chem. 2004 May 20;47(11):2728-31. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15139750 15139750]
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[[Category: Adenosine deaminase]]
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[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Kinoshita, T.]]
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[[Category: Kinoshita T]]
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[[Category: FR6]]
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[[Category: ZN]]
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[[Category: beta barrel]]
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[[Category: zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:04:58 2008''
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Current revision

Crystal structure of adenosine deaminase complexed with potent inhibitors

PDB ID 2e1w

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