1v79: Difference between revisions
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[[Image:1v79.gif|left|200px]] | [[Image:1v79.gif|left|200px]] | ||
'''Crystal structures of adenosine deaminase complexed with potent inhibitors''' | {{Structure | ||
|PDB= 1v79 |SIZE=350|CAPTION= <scene name='initialview01'>1v79</scene>, resolution 2.5Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=FR7:1-{(1R,2S)-1-[2-(2,3,-DICHLOROPHENYL)ETHYL]-2-HYDROXYPROPYL}-1H-IMIDAZOLE-4-CARBOXAMIDE'>FR7</scene> | |||
|ACTIVITY= [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] | |||
|GENE= | |||
}} | |||
'''Crystal structures of adenosine deaminase complexed with potent inhibitors''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1V79 is a [ | 1V79 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V79 OCA]. | ||
==Reference== | ==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:[http:// | 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://www.ncbi.nlm.nih.gov/pubmed/15139750 15139750] | ||
[[Category: Adenosine deaminase]] | [[Category: Adenosine deaminase]] | ||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:41:42 2008'' | ||
Revision as of 15:41, 20 March 2008
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| , resolution 2.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Adenosine deaminase, with EC number 3.5.4.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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