A hydrogen-bonding network in mammalian sorbitol dehydrogenase stabilizes the tetrameric state and is essential for the catalytic power |
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| Authors: | M Hellgren C Kaiser S de Haij Å Norberg J-O Höög |
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| Institution: | (1) Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden;(2) Present address: Biovitrum, 112 76 Stockholm, Sweden;(3) Present address: Genmab, 3508 AD Utrecht, The Netherlands |
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| Abstract: | 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.
Received 13 July 2007; received after revision 30 September 2007; accepted 1 October 2007 |
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| Keywords: | Alcohol dehydrogenase hydrogen-bonding network Gibbs energy quaternary structure sorbitol dehydrogenase structural zinc |
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