1pl8: Difference between revisions
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|PDB= 1pl8 |SIZE=350|CAPTION= <scene name='initialview01'>1pl8</scene>, resolution 1.90Å | |PDB= 1pl8 |SIZE=350|CAPTION= <scene name='initialview01'>1pl8</scene>, resolution 1.90Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <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]], [[1pl7|1PL7]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pl8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pl8 OCA], [http://www.ebi.ac.uk/pdbsum/1pl8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pl8 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Wasilko, D.]] | [[Category: Wasilko, D.]] | ||
[[Category: Watts, P.]] | [[Category: Watts, P.]] | ||
[[Category: human sorbitol dehydrogenase]] | [[Category: human sorbitol dehydrogenase]] | ||
[[Category: nad]] | [[Category: nad]] | ||
''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'' | ||
