Publications

• X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase.

  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.

  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 compl ... >> More

  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. << Less

  Structure 11:1071-1085(2003) [PubMed] [EuropePMC]

• Steady-state kinetic properties of sorbitol dehydrogenase from chicken liver.

  Karacaoglan V., Ozer I.

  The steady-state kinetic properties of partially purified chicken liver sorbitol dehydrogenase (SDH) were determined spectrophotometrically at 25 degrees C, in 50 mM 3-(N-morpholino)propanesulfonic acid (MOPS) buffer, pH 8.0. In the sorbitol-to-fructose direction, analysis was based on initial rat ... >> More

  The steady-state kinetic properties of partially purified chicken liver sorbitol dehydrogenase (SDH) were determined spectrophotometrically at 25 degrees C, in 50 mM 3-(N-morpholino)propanesulfonic acid (MOPS) buffer, pH 8.0. In the sorbitol-to-fructose direction, analysis was based on initial rate data obtained at [NAD(+)](o)=0.1-0.4 mM and [sorbitol](o)=1.25-10 mM. The reverse process was analyzed by recording progress curves for NADH consumption, starting with [NADH](o)=0.2 mM and [fructose](o)=66.7-267 mM. The kinetics conformed to an ordered sequential model, with the cofactors adding first. The steady-state parameters in the forward direction, K(NAD(+)), K(iNAD(+)) and K(sorbitol), were found to be 210+/-62 muM, 220+/-69 microM and 3.2+/-0.54 mM, respectively. The corresponding parameters in the reverse direction were K(NADH)=240+/-58 microM, K(iNADH)=10+/-2.8 microM and K(fructose)=1000+/-140 mM. The results indicated a close parallelism with human SDH, yet up to 40-fold differences were observed when compared to related reports on other mammalian species. The structural and adaptive bases of the variation in substrate and cofactor affinities need to be accounted for. << Less

  Comp. Biochem. Physiol. 140:309-312(2005) [PubMed] [EuropePMC]

• X-ray crystal structure and small-angle X-ray scattering of sheep liver sorbitol dehydrogenase.

  Yennawar H., Moller M., Gillilan R., Yennawar N.

  The X-ray crystal structure of sheep liver sorbitol dehydrogenase (slSDH) has been determined using the crystal structure of human sorbitol dehydrogenase (hSDH) as a molecular-replacement model. slSDH crystallized in space group I222 with one monomer in the asymmetric unit. A conserved tetramer th ... >> More

  The X-ray crystal structure of sheep liver sorbitol dehydrogenase (slSDH) has been determined using the crystal structure of human sorbitol dehydrogenase (hSDH) as a molecular-replacement model. slSDH crystallized in space group I222 with one monomer in the asymmetric unit. A conserved tetramer that superposes well with that seen in hSDH (despite belonging to a different space group) and obeying the 222 crystal symmetry is seen in slSDH. An acetate molecule is bound in the active site, coordinating to the active-site zinc through a water molecule. Glycerol, a substrate of slSDH, also occupies the substrate-binding pocket together with the acetate designed by nature to fit large polyol substrates. The substrate-binding pocket is seen to be in close proximity to the tetramer interface, which explains the need for the structural integrity of the tetramer for enzyme activity. Small-angle X-ray scattering was also used to identify the quaternary structure of the tetramer of slSDH in solution. << Less

  Acta Crystallogr. D 67:440-446(2011) [PubMed] [EuropePMC]

• Sorbitol dehydrogenase of Aspergillus niger, SdhA, is part of the oxido-reductive D-galactose pathway and essential for D-sorbitol catabolism.

  Koivistoinen O.M., Richard P., Penttila M., Ruohonen L., Mojzita D.

  In filamentous fungi D-galactose can be catabolised through the oxido-reductive and/or the Leloir pathway. In the oxido-reductive pathway D-galactose is converted to d-fructose in a series of steps where the last step is the oxidation of d-sorbitol by an NAD-dependent dehydrogenase. We identified ... >> More

  In filamentous fungi D-galactose can be catabolised through the oxido-reductive and/or the Leloir pathway. In the oxido-reductive pathway D-galactose is converted to d-fructose in a series of steps where the last step is the oxidation of d-sorbitol by an NAD-dependent dehydrogenase. We identified a sorbitol dehydrogenase gene, sdhA (JGI53356), in Aspergillus niger encoding a medium chain dehydrogenase which is involved in D-galactose and D-sorbitol catabolism. The gene is upregulated in the presence of D-galactose, galactitol and D-sorbitol. An sdhA deletion strain showed reduced growth on galactitol and growth on D-sorbitol was completely abolished. The purified enzyme converted D-sorbitol to D-fructose with K(m) of 50±5 mM and v(max) of 80±10 U/mg. << Less

  FEBS Lett 586:378-383(2012) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Sorbitol dehydrogenase is a cytosolic protein required for sorbitol metabolism in Arabidopsis thaliana.

  Aguayo M.F., Ampuero D., Mandujano P., Parada R., Munoz R., Gallart M., Altabella T., Cabrera R., Stange C., Handford M.

  Sorbitol is converted to fructose in Rosaceae species by SORBITOL DEHYDROGENASE (SDH, EC 1.1.1.14), especially in sink organs. SDH has also been found in non-Rosaceae species and here we show that the protein encoded by At5g51970 in Arabidopsis thaliana (L.) Heynh. possesses the molecular characte ... >> More

  Sorbitol is converted to fructose in Rosaceae species by SORBITOL DEHYDROGENASE (SDH, EC 1.1.1.14), especially in sink organs. SDH has also been found in non-Rosaceae species and here we show that the protein encoded by At5g51970 in Arabidopsis thaliana (L.) Heynh. possesses the molecular characteristics of an SDH. Using a green fluorescent protein-tagged version and anti-SDH antisera, we determined that SDH is cytosolically localized, consistent with bioinformatic predictions. We also show that SDH is widely expressed, and that SDH protein accumulates in both source and sink organs. In the presence of NAD+, recombinant SDH exhibited greatest oxidative activity with sorbitol, ribitol and xylitol as substrates; other sugar alcohols were oxidized to a lesser extent. Under standard growth conditions, three independent sdh-mutants developed as wild-type. Nevertheless, all three exhibited reduced dry weight and primary root length compared to wild-type when grown in the presence of sorbitol. Additionally, under short-day conditions, the mutants were more resistant to dehydration stress, as shown by a reduced loss of leaf water content when watering was withheld, and a greater survival rate on re-watering. This evidence suggests that limitations in the metabolism of sugar alcohols alter the growth of Arabidopsis and its response to drought. << Less

  Plant Sci. 206:63-75(2013) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Rapid affinity purification and properties of rat liver sorbitol dehydrogenase.

  Leissing N., McGuinness E.T.

  A 23-h affinity chromatography purification procedure for sorbitol dehydrogenase (L-iditol:NADl-oxidoreductase, EC 1.1.1.14) prepared from freshly excised rat liver has been developed that resulted in an 18% yield of an apparently homogeneous preparation (purification = 439-fold). The molecular we ... >> More

  A 23-h affinity chromatography purification procedure for sorbitol dehydrogenase (L-iditol:NADl-oxidoreductase, EC 1.1.1.14) prepared from freshly excised rat liver has been developed that resulted in an 18% yield of an apparently homogeneous preparation (purification = 439-fold). The molecular weight of the enzyme was approx. 96 000. The enzyme was specific for NAD+ (NADH), but had no requirement for NADP+ (NADPH). The purified preparation shows significant activity with structurally related polyols and ketoses. Km values for sorbitol and fructose are 0.35 and 110 mM (at pH 7.1), respectively. << Less

  Biochim Biophys Acta 524:254-261(1978) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.