1PL6

Human SDH/NADH/inhibitor complex

Summary for 1PL6

• Entry DOI: 10.2210/pdb1pl6/pdb
• Related: 1PL7 1PL8
• Descriptor: Sorbitol dehydrogenase, ZINC ION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: sorbitol dehydrogenase, cp-166, 572, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion membrane; Peripheral membrane protein: Q00796
• Total number of polymer chains: 4
• Total formula weight: 158538.73

Authors

Pauly, T.A.,Ekstrom, J.L.,Beebe, D.A.,Chrunyk, B.,Cunningham, D.,Griffor, M.,Kamath, A.,Lee, S.E.,Madura, R.,Mcguire, D.,Subashi, T.,Wasilko, D.,Watts, P.,Mylari, B.L.,Oates, P.J.,Adams, P.D.,Rath, V.L. (deposition date: 2003-06-07, release date: 2004-02-17, Last modification date: 2024-11-20)

Primary citation

Pauly, T.A.,Ekstrom, J.L.,Beebe, D.A.,Chrunyk, B.,Cunningham, D.,Griffor, M.,Kamath, A.,Lee, S.E.,Madura, R.,Mcguire, D.,Subashi, T.,Wasilko, D.,Watts, P.,Mylari, B.L.,Oates, P.J.,Adams, P.D.,Rath, V.L.
X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase.
Structure, 11:1071-1085, 2003

PubMed Abstract: 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.

PubMed: 12962626
DOI: 10.1016/S0969-2126(03)00167-9

Experimental method

X-RAY DIFFRACTION (2 Å)