Sorbitol Dehydrogenase

Jeffery, Jonathan; Jörnvall, Hans

doi:10.1002/9780470123072.ch2

Cited by 37 publications

(22 citation statements)

References 285 publications

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“…The close relationship between XDH and SDH is based on the following shared structural and functional characteristics: (1) presence of one, most probably catalytic, structural Zn 2+ ion per subunit, (2) a dimeric quarternary structure, and (3) the spectrum of substrates that can be oxidized or reduced. These results corroborate the conclusions of Persson et al (1993) based on a comparison of the primary structure of the P. stipitis-derived XDH with those of members of the medium-chain ADH family (Jeffery and Jo¨rnvall 1988).…”

Section: Discussionsupporting

confidence: 88%

“…In case of XDH two variants were found in the D-xylose fermenting yeast P. stipitis. One of them, the XYL2 gene product, belongs to the mediumchain alcohol dehydrogenase family that comprises mammalian sorbitol dehydrogenases (SDH), prokaryotic threonine dehydrogenases, Zn 2+ -containing alcohol dehydrogenase (ADH) and n-crystallin (Jeffery and Jo¨rnvall 1988;Persson et al 1993). In addition, a close relationship to sorbitol dehydrogenases (SDH; L-iditol: NAD À À2-oxidoreductase; EC 1.1.1.14) has been proposed (Lunzer et al 1998).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the AXDH gene and the encoded xylitol dehydrogenase from the dimorphic yeast Arxula adeninivorans

Böer¹,

Wartmann²,

Schmidt³

et al. 2005

Antonie Van Leeuwenhoek

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The xylitol dehydrogenase-encoding Arxula adeninivorans AXDH gene was isolated and characterized. The gene includes a coding sequence of 1107 bp encoding a putative 368 amino acid protein of 40.3 kDa. The identity of the gene was confirmed by a high degree of homology of the derived amino acid sequence to that of xylitol dehydrogenases from different sources. The gene activity was regulated by carbon source. In media supplemented with xylitol, D-sorbitol and D-xylose induction of the AXDH gene and intracellular accumulation of the encoded xylitol dehydrogenase was observed. This activation pattern was confirmed by analysis of AXDH promoter-GFP gene fusions. The enzyme characteristics were analysed from isolates of native strains as well as from those of recombinant strains expressing the AXDH gene under control of the strong A. adeninivorans-derived TEF1 promoter. For both proteins, a molecular mass of ca. 80 kDa was determined corresponding to a dimeric structure, an optimum pH at 7.5 and a temperature optimum at 35 degrees C. The enzyme oxidizes polyols like xylitol and D-sorbitol whereas the reduction reaction is preferred when providing D-xylulose, D-ribulose and L-sorbose as substrates. Enzyme activity exclusively depends on NAD+ or NADH as coenzymes.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Characterization of the AXDH gene and the encoded xylitol dehydrogenase from the dimorphic yeast Arxula adeninivorans

Böer¹,

Wartmann²,

Schmidt³

et al. 2005

Antonie Van Leeuwenhoek

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“…Here the importance of a correct loop structure is exposed, the rupture of which switches the quaternary structure from tetrameric to dimeric, which is the main overall structural difference between the two mammalian forms of the MDR enzymes, SDH and ADH [2,4]. Out of 88 loops in interfaces, studied in different dimers and tetramers, about 75% show hydrogen bonds with a secondary structure element from another subunit, with the majority involving mainchain groups [24].…”

Section: Discussionmentioning

confidence: 99%

“…1). The general view from structurally determined SDHs and ADHs is that the early identified deleted segment in sheep SDH and yeast ADH will favor the tetrameric structure [2,4], which is stressed from the recently determined structures [5,17,25]. Further, in vitro studies of tetrameric ADHs could verify the importance of these regions for the thermostability of the bacterial ADHs.…”

Section: Discussionmentioning

confidence: 99%

“…The functional unit of sorbitol dehydrogenase (SDH, EC 1.1.1.14) is a zinc-dependent homotetrameric enzyme [2] within the protein family of medium chain dehydrogenases/ reductases (MDR) with a close relationship to alcohol dehydrogenase (ADH, EC 1.1.1.1) [3]. The mammalian ADHs have a dimeric quaternary structure, whereas most bacterial and yeast ADHs are homotetrameric enzymes like SDH [2,[4][5][6]. The subunits of SDH are slightly smaller than the mammalian ADH subunits, with a molecular mass of 38 kDa [7].…”

Section: Introductionmentioning

confidence: 99%

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A hydrogen-bonding network in mammalian sorbitol dehydrogenase stabilizes the tetrameric state and is essential for the catalytic power

Hellgren

Kaiser

Haij

et al. 2007

Cell. Mol. Life Sci.

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Subunit interaction in sorbitol dehydrogenase (SDH) has been studied with in vitro and in silico methods identifying a vital hydrogen-bonding network, which is strictly conserved among mammalian SDH proteins. Mutation of one of the residues in the hydrogen-bonding network, Tyr110Phe, abolished the enzymatic activity and destabilized the protein into tetramers, dimers and monomers as judged from gel filtration experiments at different temperatures compared to only tetramers for the wild-type protein below 307 K. The determined equilibrium constants revealed a large difference in Gibbs energy (8 kJ/mol) for the tetramer stability between wild-type SDH and the mutated form Tyr110Phe SDH. The results focus on a network of coupled hydrogen bonds in wild-type SDH that uphold the protein interface, which is specific and favorable to electrostatic, van der Waals and hydrogen-bond interactions between subunits, interactions that are crucial for the catalytic power of SDH.

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Zn‐Dependent Medium‐Chain Dehydrogenases/Reductases

Meijers

Cedergren-Zeppezauer

2004

Handbook of Metalloproteins

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Medium‐chain dehydrogenases/reductases (MDRs) have about 350 to 390 amino acids and belong to a large superfamily of proteins including the Zn‐dependent alcohol dehydrogenases (ADHs) and several other Zn‐dependent activities. They are dimers or tetramers and utilize either NADH or NADPH as electron carriers referred to as cofactors. The oxidation/reduction process is a 2‐electron/1‐proton (hydride ion, H − ) transfer between substrate and cofactor. The compounds oxidized or reduced by these enzymes vary considerably in structure ranging from small primary and secondary alcohols/aldehydes/ketones (aliphatic and aromatic), sugars (sorbitol/fructose, glucose) to large substances like fatty acids, steroids, and retinoids. ADHs are widely distributed in nature and some MDR members are found in all species. An essential Zn ion at the active site is common to all MDRs but some members have two zinc ions per subunit. The 3D Structures of Zn‐dependent MDRs are highly similar and they essentially have the same polypeptide fold. The low sequence identity found sometimes could not immediately reveal this close structural relationship. Now numerous structures have been examined indicating that the evolutionary strategy for MDRs has been to vary amino acids preferably at the reaction center and further away in the substrate binding area. Thus, the size and shape of the substrate channel is adapted for small or large substrates, hydrophilic or hydrophobic substances, modifications attained via few mutations, or significant deletions/additions of amino acids. A further opportunity to create multiplicity has been to vary the control mechanism for the protein conformation change and the oligomeric state. Some enzymes undergo significant structural changes upon cofactor binding, while others do not. A transition state intermediate of NADH in complex with horse liver alcohol dehydrogenase, resolved to atomic resolution (≈1 Å), has revealed structural modifications of the cofactor associated with the activation process for hydride transfer. This involves an OH − pyridine ring adduct, connected to the zinc center. The distortion of the nicotinamide at the enzyme site, affected by the presence of the negatively charged oxygen ligand, influences three parameters: (i) the puckering of the ring, (ii) a deviation from a standard carbon–carbon double bond length, and (iii) accumulation of negative charge at the C4 atom promoting hydride transfer. The active site Zn‐center of this large enzyme group shows great flexibility with respect to metal–ligand geometry and dynamics. Structural and spectroscopic evidence suggest that Zn‐dependent MDRs should be included in the general family of Zn‐enzymes, which require water and hydroxide ion as reactants during catalysis.

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Sorbitol Dehydrogenase

Cited by 37 publications

References 285 publications

Characterization of the AXDH gene and the encoded xylitol dehydrogenase from the dimorphic yeast Arxula adeninivorans

Characterization of the AXDH gene and the encoded xylitol dehydrogenase from the dimorphic yeast Arxula adeninivorans

A hydrogen-bonding network in mammalian sorbitol dehydrogenase stabilizes the tetrameric state and is essential for the catalytic power

Zn‐Dependent Medium‐Chain Dehydrogenases/Reductases

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