2e1w

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[[Image:2e1w.gif|left|200px]]<br /><applet load="2e1w" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2e1w.gif|left|200px]]
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caption="2e1w, resolution 2.5&Aring;" />
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'''Crystal structure of adenosine deaminase complexed with potent inhibitors'''<br />
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{{Structure
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|PDB= 2e1w |SIZE=350|CAPTION= <scene name='initialview01'>2e1w</scene>, resolution 2.5&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=FR6:1-{(1R,2S)-2-HYDROXY-1-[2-(1-NAPHTHYL)ETHYL]PROPYL}-1H-IMIDAZOLE-4-CARBOXAMIDE'>FR6</scene>
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|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]
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|GENE=
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}}
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'''Crystal structure of adenosine deaminase complexed with potent inhibitors'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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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].
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2E1W is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. This structure supersedes the now removed PDB entry 1V78. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E1W OCA].
==Reference==
==Reference==
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=15139750 15139750]
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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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:04:58 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:34:10 2008''

Revision as of 14:34, 20 March 2008

Image:2e1w.gif


PDB ID 2e1w

Drag the structure with the mouse to rotate
, resolution 2.5Å
Ligands: and
Activity: Adenosine deaminase, with EC number 3.5.4.4
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

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