1pl8

File:1pl8.gif

spinqualitylabelsall models PDB ID 1pl8 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 1.90Å
Ligands:	and
Activity:	L-iditol 2-dehydrogenase, with EC number 1.1.1.14
Coordinates:	save as pdb, mmCIF, xml

human SDH/NAD+ complex

OverviewOverview

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.

DiseaseDisease

Known disease associated with this structure: Cataract, congenital (2) OMIM:[182500]

About this StructureAbout this Structure

1PL8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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

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