2e1w: Difference between revisions
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==Crystal structure of adenosine deaminase complexed with potent inhibitors== | ==Crystal structure of adenosine deaminase complexed with potent inhibitors== | ||
<StructureSection load='2e1w' size='340' side='right' caption='[[2e1w]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='2e1w' size='340' side='right' caption='[[2e1w]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1v79|1v79]], [[1v7a|1v7a]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1v79|1v79]], [[1v7a|1v7a]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2e1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e1w OCA], [http://pdbe.org/2e1w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2e1w RCSB], [http://www.ebi.ac.uk/pdbsum/2e1w PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2e1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e1w OCA], [http://pdbe.org/2e1w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2e1w RCSB], [http://www.ebi.ac.uk/pdbsum/2e1w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2e1w ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e1/2e1w_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e1/2e1w_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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[[Category: Beta barrel]] | [[Category: Beta barrel]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Zinc]] | |||
Revision as of 09:41, 6 June 2018
Crystal structure of adenosine deaminase complexed with potent inhibitorsCrystal structure of adenosine deaminase complexed with potent inhibitors
Structural highlights
Function[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). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe 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. 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:15139750[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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