1pl7
From Proteopedia
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|PDB= 1pl7 |SIZE=350|CAPTION= <scene name='initialview01'>1pl7</scene>, resolution 2.20Å | |PDB= 1pl7 |SIZE=350|CAPTION= <scene name='initialview01'>1pl7</scene>, resolution 2.20Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1pl6|1PL6]], [[1pl8|1PL8]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pl7 OCA], [http://www.ebi.ac.uk/pdbsum/1pl7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pl7 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known disease associated with this structure: Cataract, congenital (2) OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=182500 182500]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Wasilko, D.]] | [[Category: Wasilko, D.]] | ||
[[Category: Watts, P.]] | [[Category: Watts, P.]] | ||
| - | [[Category: ZN]] | ||
[[Category: human sorbitol dehydrogenase]] | [[Category: human sorbitol dehydrogenase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:01:13 2008'' |
Revision as of 20:01, 30 March 2008
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| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | L-iditol 2-dehydrogenase, with EC number 1.1.1.14 | ||||||
| Related: | 1PL6, 1PL8
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human Sorbitol Dehydrogenase (apo)
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.
About this Structure
1PL7 is a Single protein structure of sequence from Homo sapiens. 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 Sun Mar 30 23:01:13 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. | Human sorbitol dehydrogenase
