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1n5x

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(New page: 200px<br /><applet load="1n5x" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n5x, resolution 2.80&Aring;" /> '''Xanthine Dehydrogena...)
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[[Image:1n5x.gif|left|200px]]<br /><applet load="1n5x" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1n5x, resolution 2.80&Aring;" />
 
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'''Xanthine Dehydrogenase from Bovine Milk with Inhibitor TEI-6720 Bound'''<br />
 
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==Overview==
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==Xanthine Dehydrogenase from Bovine Milk with Inhibitor TEI-6720 Bound==
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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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<StructureSection load='1n5x' size='340' side='right'caption='[[1n5x]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1n5x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N5X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N5X FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=MOS:DIOXOTHIOMOLYBDENUM(VI)+ION'>MOS</scene>, <scene name='pdbligand=MTE:PHOSPHONIC+ACIDMONO-(2-AMINO-5,6-DIMERCAPTO-4-OXO-3,7,8A,9,10,10A-HEXAHYDRO-4H-8-OXA-1,3,9,10-TETRAAZA-ANTHRACEN-7-YLMETHYL)ESTER'>MTE</scene>, <scene name='pdbligand=TEI:2-(3-CYANO-4-ISOBUTOXY-PHENYL)-4-METHYL-5-THIAZOLE-CARBOXYLIC+ACID'>TEI</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1n5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n5x OCA], [https://pdbe.org/1n5x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n5x RCSB], [https://www.ebi.ac.uk/pdbsum/1n5x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n5x ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/XDH_BOVIN XDH_BOVIN] Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n5/1n5x_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1n5x ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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==
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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<ref>PMID:12421831</ref>
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1N5X 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 FES, MTE, MOS, FAD and TEI as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Xanthine_dehydrogenase Xanthine dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.1.4 1.17.1.4] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1N5X OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12421831 12421831]
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</div>
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[[Category: Bos taurus]]
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<div class="pdbe-citations 1n5x" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Xanthine dehydrogenase]]
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[[Category: Eger, B.T.]]
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[[Category: Kondo, S.]]
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[[Category: Nishino, T.]]
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[[Category: Okamoto, K.]]
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[[Category: Pai, E.F.]]
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[[Category: FAD]]
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[[Category: FES]]
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[[Category: MOS]]
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[[Category: MTE]]
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[[Category: TEI]]
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[[Category: 3d-structure]]
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[[Category: fad]]
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[[Category: fe2/s2 center]]
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[[Category: flavoprotein]]
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[[Category: iron-sulfur center]]
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[[Category: molybdopterin]]
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[[Category: oxidoreductase]]
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[[Category: tei-6720]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:59:18 2007''
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==See Also==
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*[[Xanthine dehydrogenase|Xanthine dehydrogenase]]
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*[[Xanthine dehydrogenase 3D structures|Xanthine dehydrogenase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Bos taurus]]
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[[Category: Large Structures]]
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[[Category: Eger BT]]
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[[Category: Kondo S]]
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[[Category: Nishino T]]
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[[Category: Okamoto K]]
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[[Category: Pai EF]]

Current revision

Xanthine Dehydrogenase from Bovine Milk with Inhibitor TEI-6720 Bound

PDB ID 1n5x

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