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Inhibition of Nicotinoprotein (NAD+-Containing) Alcohol Dehydrogenase by trans-4-(N,N-Dimethylamino)-Cinnamaldehyde Binding to the Active Site

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Abstract

Ethanol oxidation by nicotinoprotein alcohol dehydrogenase (np-ADH) from the bacterium Amycolatopsis methanolica is inhibited by trans-4-(N,N-dimethylamino)-cinnamaldehyde through direct binding to the catalytic zinc ion in a substrate-like geometry. This binding is accompanied by a characteristic red shift of the aldehyde absorbance from 398 nm to 467 nm. Np-ADH is structurally related to mammalian ADH class I, and a model of np-ADH shows how the cinnamaldehyde derivative can be accommodated in the active site of the nicotinoprotein, correlating the structural and enzymological data.

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REFERENCES

  • Cedergren-Zeppezauer, E., Samama, J.-P., and Eklund, H. (1982). Crystal structure determinations of coenzyme analogue and substrate complexes of liver alcohol dehydrogenase: Binding of 1,4,5,6-tetrahydronicotinamide adenine dinucleotide and trans-4-(N,N-dimethylamino)cinnamaldehyde to the enzyme. Biochemistry 21: 4895–4908.

    Article  CAS  PubMed  Google Scholar 

  • Cornish-Bowden, A. (1995). Analysis of enzyme kinetic data, p. 198, Oxford University press, Oxford.

    Google Scholar 

  • Dahl, K. H., and Dunn, M. F. (1984). Reaction of 4-trans-(N,Ndimethylamino) cinnamaldehyde with the liver alcohol dehydrogenase-oxidized nicotinamide adenine dinucleotide complex. Biochemistry 23: 4094–4100.

    Article  CAS  PubMed  Google Scholar 

  • Dietrich, H., Maret, W., Wallén, L., and Zeppezauer, M. (1979). Active-site-specific reconstituted cobalt(II) horse-liver alcohol dehydrogenase. Changes of the spectra of the substrate trans-4-(N,N-dimethylamino)-cinnamaldehyde and of the catalytic cobalt ion upon ternary complex formation with NADH and 1,4,5,6-tetrahydronicotinamide-adenine dinucleotide. Eur J Biochem. 100: 267–270.

    Article  CAS  PubMed  Google Scholar 

  • Dunn, M. F., and Bernhard, S. A. (1971). Rapid kinetic evidence for adduct formation between the substrate analog p-nitroso-N,Ndimethylaniline and reduced nicotinamide-adenine dinucleotide during enzymic reduction. Biochemistry 10: 4569–4575.

    Article  CAS  PubMed  Google Scholar 

  • Dunn, M. F., and Hutchinson, J. S. (1973). Roles of zinc ion and reduced coenzyme in the formation of a transient chemical intermediate during the equine liver alcohol dehydrogenase catalyzed reduction of an aromatic aldehyde. Biochemistry 12: 4882–4892.

    Article  CAS  PubMed  Google Scholar 

  • Dunn, M. F., Dietrich, H., MacGibbon, A. K. H., Koerber, S. C., and Zeppezauer, M. (1982). Investigation of intermediates and transition states in the catalytic mechanisms of active site substituted cobalt(II), nickel(II), zinc(II), and cadmium(II) horse liver alcohol dehydrogenase. Biochemistry 21: 354–363.

    Article  CAS  PubMed  Google Scholar 

  • Eklund, H., Müller-Wille, P., Horjales, E., Futer, O., Holmquist, B., Vallee, B.L., Höög, J.-O., Kaiser, R., and Jörnvall, H. (1990). Comparison of three classes of human liver alcohol dehydrogenase. Emphasis on different substrate-binding pockets. Eur. J. Biochem. 193: 303–310.

    Article  CAS  PubMed  Google Scholar 

  • Jörnvall, H., Nordling, E., and Persson, B. (2003). Multiplicity of eukaryotic ADH and other MDR forms. Chem.-Biol. Interact. 143–144: 255–261.

    Article  PubMed  Google Scholar 

  • Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685.

    Article  CAS  PubMed  Google Scholar 

  • Norin, A., Piersma, S. R., Duine, J. A., and Jörnvall, H. (2003). Nicotinoprotein (NAD+-containing) alcohol dehydrogenase: Structural relationships and functional interpretations. Cell. Mol. Life Sci. 60: in press.

  • Piersma, S. R., Visser, A. J. W. G., de Vries, S., and Duine, J. A. (1998). Optical spectroscopy of nicotinoprotein alcohol dehydrogenase from Amycolatopsis methanolica: A comparison with horse liver alcohol dehydrogenase and UDP-galactose epimerase. Biochemistry 37: 3068–3077.

    Article  CAS  PubMed  Google Scholar 

  • Ramaswamy, S., Eklund, H., and Plapp, B. V. (1994). Structures of horse liver alcohol dehydrogenase complexed with NAD+ and substituted benzyl alcohols. Biochemistry 33: 5230–5237.

    Article  CAS  PubMed  Google Scholar 

  • Schneider-Bernlöhr, H., Formicka-Kozlowska, G., Bühler, R., von Wartburg, J.-P., and Zeppezauer, M. (1988). Active-site-specific zinc-depleted and reconstituted cobalt(II) human-liver alcohol dehydrogenase. Preparation, characterization and complexation with NADH and trans-4-(N,N-dimethylamino)-cinnamaldehyde. Eur. J. Biochem. 173: 275–280.

    Article  PubMed  Google Scholar 

  • Stone, C. L., Bosron, W. F., and Dunn, M. F. (1993). Amino acid substitutions at position 47 of human β1β1 and β2β2 alcohol dehydrogenases affect hydride transfer and coenzyme dissociation rate constants. J. Biol. Chem. 268: 892–899.

    Article  CAS  PubMed  Google Scholar 

  • van Ophem, P. W., van Beeumen, J., and Duine, J. A. (1993). Nicotinoprotein 'NAD(P)-containing' alcohol/aldehyde oxidoreductases. Purification and characterization of a novel type from Amycolatopsis methanolica. Eur. J. Biochem. 156: 819–826.

    Article  Google Scholar 

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Author notes

  1. Sander R. Piersma

    Present address: FOM-Institute for Atomic and Molecular Physics (AMOLF), 1098 SJ, Amsterdam, the Netherlands

Authors and Affiliations

  1. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77, Stockholm, Sweden

    Sander R. Piersma, Annika Norin & Hans Jörnvall

  2. Department of Microbiology and Enzymology, Delft University of Technology, NL-2628 BC, Delft, the Netherlands

    Sander R. Piersma, Simon de Vries & Johannis A. Duine

Authors
  1. Sander R. Piersma
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  2. Annika Norin
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  3. Simon de Vries
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  4. Hans Jörnvall
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  5. Johannis A. Duine
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Corresponding author

Correspondence to Hans Jörnvall.

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Piersma, S.R., Norin, A., de Vries, S. et al. Inhibition of Nicotinoprotein (NAD+-Containing) Alcohol Dehydrogenase by trans-4-(N,N-Dimethylamino)-Cinnamaldehyde Binding to the Active Site. J Protein Chem 22, 457–461 (2003). https://doi.org/10.1023/B:JOPC.0000005461.53788.ee

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  • DOI: https://doi.org/10.1023/B:JOPC.0000005461.53788.ee

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