Structure of human β1β1 alcohol dehydrogenase: Catalytic effects of non-active-site substitutions

Thomas D. Hurley, William F. Bosron, Jean A. Hamilton, L. Mario Amzel

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


The three-dimensional structure of human β1β1 alcohol dehydrogenase (ADH; EC complexed with NAD+ has been determined by x-ray crystallography to 3.0-Å resolution. The amino adds directly involved in coenzyme binding are conserved between horse EE and human β1β1 alcohol dehydrogenase in all but one case [serine (horse) vs. threonine (human) at position 48]. As a result, the coenzyme molecule is bound in a similar manner in the two enzymes. However, the strength of the interactions in the vicinity of the pyrophosphate bridge of NAD+ appears to be enhanced in the human enzyme. Side-chain movements of Arg-47 and Asp-50 and a shift in the position of the helix comprising residues 202-212 may explain both the decreased Vmax, and the decreased rate of NADH dissociation observed in the human enzyme vs. the horse enzyme. It appears that these catalytic differences are not due to substitutions of any amino acids directly involved in coenzyme binding but are the result of structural rearrangements resulting from multiple sequence differences between the two enzymes. (.

Original languageEnglish (US)
Pages (from-to)8149-8153
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number18
StatePublished - 1991


  • Enzyme-cofactor complex/
  • Nad
  • X-ray diffraction/

ASJC Scopus subject areas

  • General


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