1pl7
From Proteopedia
(New page: 200px<br /> <applet load="1pl7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pl7, resolution 2.20Å" /> '''Human Sorbitol Dehy...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1pl7.gif|left|200px]]<br /> | + | [[Image:1pl7.gif|left|200px]]<br /><applet load="1pl7" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1pl7" size=" | + | |
caption="1pl7, resolution 2.20Å" /> | caption="1pl7, resolution 2.20Å" /> | ||
'''Human Sorbitol Dehydrogenase (apo)'''<br /> | '''Human Sorbitol Dehydrogenase (apo)'''<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== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1PL7 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 as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 1PL7 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> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1PL7 OCA]. |
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[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.]] | ||
| Line 38: | Line 37: | ||
[[Category: human sorbitol dehydrogenase]] | [[Category: human sorbitol dehydrogenase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:29:59 2008'' |
Revision as of 12:30, 21 February 2008
|
Human Sorbitol Dehydrogenase (apo)
Contents |
Overview
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
Known disease associated with this structure: Cataract, congenital (2) OMIM:[182500]
About this Structure
1PL7 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as L-iditol 2-dehydrogenase, with EC number 1.1.1.14 Full crystallographic information is available from OCA.
Reference
X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase., Pauly TA, Ekstrom JL, Beebe DA, Chrunyk B, Cunningham D, Griffor M, Kamath A, Lee SE, Madura R, Mcguire D, Subashi T, Wasilko D, Watts P, Mylari BL, Oates PJ, Adams PD, Rath VL, Structure. 2003 Sep;11(9):1071-85. PMID:12962626
Page seeded by OCA on Thu Feb 21 14:29:59 2008
Categories: Homo sapiens | L-iditol 2-dehydrogenase | Single protein | Adams, P D. | Beebe, D A. | Chrunyk, B. | Cunningham, D. | Ekstrom, J L. | Griffor, M. | Kamath, A. | Lee, S E. | Madura, R. | Mcguire, D. | Mylari, B L. | Oates, P J. | Pauly, T A. | Rath, V L. | Subashi, T. | Wasilko, D. | Watts, P. | ZN | Human sorbitol dehydrogenase
