PMID: 8460164Mar 15, 1993Paper

Mutation of Arg-115 of human class III alcohol dehydrogenase: a binding site required for formaldehyde dehydrogenase activity and fatty acid activation

Proceedings of the National Academy of Sciences of the United States of America
K EngelandB L Vallee

Abstract

The origin of the fatty acid activation and formaldehyde dehydrogenase activity that distinguishes human class III alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) from all other alcohol dehydrogenases has been examined by site-directed mutagenesis of its Arg-115 residue. The Ala- and Asp-115 mutant proteins were expressed in Escherichia coli and purified by affinity chromatography and ion-exchange HPLC. The activities of the recombinant native and mutant enzymes toward ethanol are essentially identical, but mutagenesis greatly decreases the kcat/Km values for glutathione-dependent formaldehyde oxidation. The catalytic efficiency for the Asp variant is < 0.1% that of the unmutated enzyme, due to both a higher Km and a lower kcat value. As with the native enzyme, neither mutant can oxidize methanol, be saturated by ethanol, or be inhibited by 4-methylpyrazole; i.e., they retain these class III characteristics. In contrast, however, their activation by fatty acids, another characteristic unique to class III alcohol dehydrogenase, is markedly attenuated. The Ala mutant is activated only slightly, but the Asp mutant is not activated at all. The results strongly indicate that Arg-115 in class III alcohol dehydrogenase...Continue Reading

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Oct 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·O Danielsson, H Jörnvall
Aug 15, 1991·Biochemical and Biophysical Research Communications·B Holmquist, B L Vallee
Sep 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·M YasunamiA Yoshida
Oct 31, 1989·Biochemical and Biophysical Research Communications·C P SharmaB L Vallee

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Citations

Jan 24, 2009·European Archives of Psychiatry and Clinical Neuroscience·Daniel Martins-de-SouzaChristoph W Turck
Jul 15, 2009·The Journal of Biological Chemistry·Paresh C SanghaniSonal P Sanghani
Apr 20, 2011·Virology Journal·Rajagowthamee R ThangavelStephen J Stray
Apr 21, 2010·Cellular and Molecular Life Sciences : CMLS·Mikko HellgrenJan-Olov Höög
Feb 27, 2003·Chemico-biological Interactions·Paresh C SanghaniW F Bosron
Jun 28, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Matej KravosSuzana Levanic
Apr 11, 2017·Critical Reviews in Biochemistry and Molecular Biology·Scott D Barnett, Iain L O Buxton
Aug 16, 1993·FEBS Letters·M Rosario FernándezX Parés
May 23, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Chad M ThompsonRoland C Grafström
Nov 14, 2019·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Xiangpei YueZhiqian Tong
Jun 5, 2014·The Journal of Biological Chemistry·Kaiyuan WuChang Chen
Mar 30, 2021·The Biochemical Journal·Roman V LenchineChristopher G Proud
Oct 16, 2021·Comprehensive Reviews in Food Science and Food Safety·Mathieu SchwartzFrancis Canon

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