The human β3 alcohol dehydrogenase subunit differs from β1 by a cys for Arg-369 substitution which decreases NAD(H) binding

Joe C. Burnell, Lucinda G. Carr, Francis E. Dwulet, Howard J. Edenberg, Ting Kai Li, William F. Bosron

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Abstract

The β3β3 (formerly called βIndianapolis) and β1β1 isoenzymes of human alcohol dehydrogenase differ substantially in their catalytic properties. Specifically, the KM value for NAD+ of β3β3 is 70 times greater than that of β1β1, and the Ki value for NADH is 35 times greater than that of β1β1. To identify the structural basis of these catalytic differences, we sequenced regions of the β3 subunit and the β3 gene. β3 differs from β1 by the substitution of Cys for Arg-369. Based on x-ray crystallography of horse ADH, Arg-369 should interact with the nicotinamide phosphate moiety of NAD(H). The Cys for Arg-369 substitution would decrease the enzyme's affinity for coenzyme and, thus, account for the observed kinetic differences between β3β3 and β1β1.

Original languageEnglish (US)
Pages (from-to)1227-1233
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume146
Issue number3
DOIs
StatePublished - Aug 14 1987

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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