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1ndv

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[[Image:1ndv.jpg|left|200px]]<br /><applet load="1ndv" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ndv, resolution 2.3&Aring;" />
 
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'''Crystal Structure of Adenosine Deaminase complexed with FR117016'''<br />
 
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==Overview==
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==Crystal Structure of Adenosine Deaminase complexed with FR117016==
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We disclose herein the rapid discovery of the first highly potent (Ki = 7.7 nM) non-nucleoside adenosine deaminase (ADA) inhibitor based on the rational hybridization of two structurally distinct leads. Two micromolar inhibitors were discovered by a parallel rational design and random screening program, and individual crystal structures of bovine ADA in complexation with these inhibitors revealed several unknown binding sites and distinct binding modes. Using this information as the starting point, highly effective lead hybridization was achieved in only two structure-based drug design iterations. The conceptual approach illustrated by this example promises to be broadly useful in the search for new chemical entities and can contribute greatly to improve the overall efficiency and speed of drug discovery.
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<StructureSection load='1ndv' size='340' side='right'caption='[[1ndv]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1ndv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NDV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NDV 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]] 2.3&#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=FR0:N-(4-(5-((1H-BENZIMIDAZOL-2-YLAMINO)METHYL)-2-THIENYL)-1,3-THIAZOL-2-YL)GUANIDINE'>FR0</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=1ndv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ndv OCA], [https://pdbe.org/1ndv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ndv RCSB], [https://www.ebi.ac.uk/pdbsum/1ndv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ndv 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/nd/1ndv_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=1ndv 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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1NDV 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=FR0:'>FR0</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1NDV 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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A highly potent non-nucleoside adenosine deaminase inhibitor: efficient drug discovery by intentional lead hybridization., Terasaka T, Kinoshita T, Kuno M, Nakanishi I, J Am Chem Soc. 2004 Jan 14;126(1):34-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14709046 14709046]
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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: FR0]]
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[[Category: ZN]]
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[[Category: beta barrel]]
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[[Category: inhibitor-induced conformational change]]
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[[Category: structure-based drug design]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:05:03 2008''
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Current revision

Crystal Structure of Adenosine Deaminase complexed with FR117016

PDB ID 1ndv

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