2e1w
From Proteopedia
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|PDB= 2e1w |SIZE=350|CAPTION= <scene name='initialview01'>2e1w</scene>, resolution 2.5Å | |PDB= 2e1w |SIZE=350|CAPTION= <scene name='initialview01'>2e1w</scene>, resolution 2.5Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=FR6:1-{(1R,2S)-2-HYDROXY-1-[2-(1-NAPHTHYL)ETHYL]PROPYL}-1H-IMIDAZOLE-4-CARBOXAMIDE'>FR6</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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] | + | |ACTIVITY= <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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1v79|1V79]], [[1v7a|1V7A]] | ||
| + | |RESOURCES=<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://www.ebi.ac.uk/pdbsum/2e1w PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2e1w RCSB]</span> | ||
}} | }} | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Kinoshita, T.]] | [[Category: Kinoshita, T.]] | ||
| - | [[Category: FR6]] | ||
| - | [[Category: ZN]] | ||
[[Category: beta barrel]] | [[Category: beta barrel]] | ||
[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:42:28 2008'' |
Revision as of 23:42, 30 March 2008
| |||||||
| , resolution 2.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Adenosine deaminase, with EC number 3.5.4.4 | ||||||
| Related: | 1V79, 1V7A
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. This structure supersedes the now removed PDB entry 1V78. 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 Mon Mar 31 02:42:28 2008
