1pl6: Difference between revisions
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New page: left|200px<br /> <applet load="1pl6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pl6, resolution 2.00Å" /> '''Human SDH/NADH/inhi... |
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[[Image:1pl6.gif|left|200px]]<br /> | [[Image:1pl6.gif|left|200px]]<br /><applet load="1pl6" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1pl6" size=" | |||
caption="1pl6, resolution 2.00Å" /> | caption="1pl6, resolution 2.00Å" /> | ||
'''Human SDH/NADH/inhibitor complex'''<br /> | '''Human SDH/NADH/inhibitor complex'''<br /> | ||
==Overview== | ==Overview== | ||
Sorbitol dehydrogenase (hSDH) and aldose reductase form the polyol pathway | Sorbitol dehydrogenase (hSDH) and aldose reductase form the polyol pathway that interconverts glucose and fructose. Redox changes from overproduction of the coenzyme NADH by SDH may play a role in diabetes-induced dysfunction in sensitive tissues, making SDH a therapeutic target for diabetic complications. We have purified and determined the crystal structures of human SDH alone, SDH with NAD(+), and SDH with NADH and an inhibitor that is competitive with fructose. hSDH is a tetramer of identical, catalytically active subunits. In the apo and NAD(+) complex, the catalytic zinc is coordinated by His69, Cys44, Glu70, and a water molecule. The inhibitor coordinates the zinc through an oxygen and a nitrogen atom with the concomitant dissociation of Glu70. The inhibitor forms hydrophobic interactions to NADH and likely sterically occludes substrate binding. The structure of the inhibitor complex provides a framework for developing more potent inhibitors of hSDH. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1PL6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, NAD and 572 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/L-iditol_2-dehydrogenase L-iditol 2-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.14 1.1.1.14] Full crystallographic information is available from [http:// | 1PL6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=NAD:'>NAD</scene> and <scene name='pdbligand=572:'>572</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/L-iditol_2-dehydrogenase L-iditol 2-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.14 1.1.1.14] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PL6 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: L-iditol 2-dehydrogenase]] | [[Category: L-iditol 2-dehydrogenase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Adams, P | [[Category: Adams, P D.]] | ||
[[Category: Beebe, D | [[Category: Beebe, D A.]] | ||
[[Category: Chrunyk, B.]] | [[Category: Chrunyk, B.]] | ||
[[Category: Cunningham, D.]] | [[Category: Cunningham, D.]] | ||
[[Category: Ekstrom, J | [[Category: Ekstrom, J L.]] | ||
[[Category: Griffor, M.]] | [[Category: Griffor, M.]] | ||
[[Category: Kamath, A.]] | [[Category: Kamath, A.]] | ||
[[Category: Lee, S | [[Category: Lee, S E.]] | ||
[[Category: Madura, R.]] | [[Category: Madura, R.]] | ||
[[Category: Mcguire, D.]] | [[Category: Mcguire, D.]] | ||
[[Category: Mylari, B | [[Category: Mylari, B L.]] | ||
[[Category: Oates, P | [[Category: Oates, P J.]] | ||
[[Category: Pauly, T | [[Category: Pauly, T A.]] | ||
[[Category: Rath, V | [[Category: Rath, V L.]] | ||
[[Category: Subashi, T.]] | [[Category: Subashi, T.]] | ||
[[Category: Wasilko, D.]] | [[Category: Wasilko, D.]] | ||
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[[Category: NAD]] | [[Category: NAD]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: cp-166]] | [[Category: cp-166]] | ||
[[Category: sorbitol dehydrogenase]] | [[Category: sorbitol dehydrogenase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:29:57 2008'' | ||
