Structural analysis of the acetaldehyde dehydrogenase activity of Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2), a member of the ADHE enzyme family.
The ADHE family of enzymes are bifunctional acetaldehyde dehydrogenase (ALDH)/alcohol dehydrogenase (ADH) enzymes that probably arose from the fusion of genes encoding separate ALDH and ADH enzymes. Here we have used the Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) enzyme as a prototype to analyze the structure and function of the ALDH domain of ADHE enzymes. We find that the N-terminal domain of EhADH2, encompassing amino acids 1-446, is sufficient for ALDH activity, consistent with the concept that EhADH2, and other members of the ADHE family comprise fusion peptides. In addition, we show, using site directed mutagenesis, that the catalytic mechanism for the ALDH activity appears to be similar to that described for other members of the ALDH extended family.
Chen
Minghe
M
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Li
Ellen
E
Stanley
Samuel L
SL
D000426:Alcohol Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D004748:Entamoeba histolytica / Q000201:enzymology* / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D017125:Genes, Protozoan; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D029968:Escherichia coli Proteins; D009097:Multienzyme Complexes; D011994:Recombinant Proteins; D000426:Alcohol Dehydrogenase; C068383:adhE protein, E coli; D000445:Aldehyde Oxidoreductases