1v79: Difference between revisions
New page: left|200px<br /><applet load="1v79" size="450" color="white" frame="true" align="right" spinBox="true" caption="1v79, resolution 2.5Å" /> '''Crystal structures of... |
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[[Image:1v79.gif|left|200px]]<br /><applet load="1v79" size=" | [[Image:1v79.gif|left|200px]]<br /><applet load="1v79" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1v79, resolution 2.5Å" /> | caption="1v79, resolution 2.5Å" /> | ||
'''Crystal structures of adenosine deaminase complexed with potent inhibitors'''<br /> | '''Crystal structures of adenosine deaminase complexed with potent inhibitors'''<br /> | ||
==Overview== | ==Overview== | ||
We disclose optimization efforts based on the novel non-nucleoside | 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. | ||
==About this Structure== | ==About this Structure== | ||
1V79 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 ZN and FR7 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:// | 1V79 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=FR7:'>FR7</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=1V79 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:32:16 2008'' | ||
Revision as of 16:32, 21 February 2008
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Crystal structures of adenosine deaminase complexed with potent inhibitors
OverviewOverview
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.
About this StructureAbout this Structure
1V79 is a Single protein structure of sequence from Bos taurus with and as ligands. Active as Adenosine deaminase, with EC number 3.5.4.4 Full crystallographic information is available from OCA.
ReferenceReference
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
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