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1n5x

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[[Image:1n5x.gif|left|200px]]
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{{STRUCTURE_1n5x| PDB=1n5x | SCENE= }}
{{STRUCTURE_1n5x| PDB=1n5x | SCENE= }}
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'''Xanthine Dehydrogenase from Bovine Milk with Inhibitor TEI-6720 Bound'''
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===Xanthine Dehydrogenase from Bovine Milk with Inhibitor TEI-6720 Bound===
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==Overview==
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TEI-6720 (2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid) is an extremely potent inhibitor of xanthine oxidoreductase. Steady state kinetics measurements exhibit mixed type inhibition with K(i) and K(i)' values of 1.2 +/- 0.05 x 10(-10) m and 9 +/- 0.05 x 10(-10) m, respectively. Fluorescence-monitored titration experiments showed that TEI-6720 bound very tightly to both the active and the inactive desulfo-form of the enzyme. The dissociation constant determined for the desulfo-form was 2 +/- 0.03 x 10(-9) m; for the active form, the corresponding number was too low to allow accurate measurements. The crystal structure of the active sulfo-form of milk xanthine dehydrogenase complexed with TEI-6720 and determined at 2.8-A resolution revealed the inhibitor molecule bound in a long, narrow channel leading to the molybdenum-pterin active site of the enzyme. It filled up most of the channel and the immediate environment of the cofactor, very effectively inhibiting the activity of the enzyme through the prevention of substrate binding. Although the inhibitor did not directly coordinate to the molybdenum ion, numerous hydrogen bonds as well as hydrophobic interactions with the protein matrix were observed, most of which are also used in substrate recognition.
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==About this Structure==
==About this Structure==
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[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
[[Category: Tei-6720]]
[[Category: Tei-6720]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:08:03 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 11:31:11 2008''

Revision as of 08:31, 29 July 2008

Image:1n5x.png

Template:STRUCTURE 1n5x

Xanthine Dehydrogenase from Bovine Milk with Inhibitor TEI-6720 Bound

Template:ABSTRACT PUBMED 12421831

About this Structure

1N5X is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.

Reference

An extremely potent inhibitor of xanthine oxidoreductase. Crystal structure of the enzyme-inhibitor complex and mechanism of inhibition., Okamoto K, Eger BT, Nishino T, Kondo S, Pai EF, Nishino T, J Biol Chem. 2003 Jan 17;278(3):1848-55. Epub 2002 Nov 5. PMID:12421831

Page seeded by OCA on Tue Jul 29 11:31:11 2008

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