2e1w
From Proteopedia
(New page: 200px<br /><applet load="2e1w" size="450" color="white" frame="true" align="right" spinBox="true" caption="2e1w, resolution 2.5Å" /> '''Crystal structure of ...) |
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| - | [[Image:2e1w.gif|left|200px]]<br /><applet load="2e1w" size=" | + | [[Image:2e1w.gif|left|200px]]<br /><applet load="2e1w" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2e1w, resolution 2.5Å" /> | caption="2e1w, resolution 2.5Å" /> | ||
'''Crystal structure of adenosine deaminase complexed with potent inhibitors'''<br /> | '''Crystal structure 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== | ||
| - | 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 ZN and FR6 as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | + | 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]. |
==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 17:04:58 2008'' |
Revision as of 15:05, 21 February 2008
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Crystal structure of adenosine deaminase complexed with potent inhibitors
Overview
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
2E1W is a Single protein structure of sequence from Bos taurus with and as ligands. This structure supersedes the now removed PDB entry 1V78. Active as Adenosine deaminase, with EC number 3.5.4.4 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 17:04:58 2008
Categories: Adenosine deaminase | Bos taurus | Single protein | Kinoshita, T. | FR6 | ZN | Beta barrel | Zinc
