2e1w

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Revision as of 07:47, 21 November 2007

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spinqualitylabelsall models 2e1w, resolution 2.5Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 ZN and FR6 as ligands. This structure superseeds 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

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