Atypical human liver alcohol dehydrogenase: the beta 2-Bern subunit has an amino acid exchange that is identical to the one in the beta 2-Oriental chain |
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Authors: | Rolf Bühler John Hempel Jean-Pierre von Wartburg Hans Jörnvall |
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Institution: | 1. Medizinisch-Chemisches Institut der Universität Bern, CH-3000 Bern 9, Switzerland;2. Department of Chemistry I, Karolinska Institutet, S-104 01 Stockholm, Sweden |
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Abstract: | The "atypical' human liver alcohol dehydrogenase dimer, homogeneous for beta 2-Bern chains, was isolated from human liver of Caucasian individuals. It is derived from an allelic variant at the ADH2 gene locus and exhibits a considerably higher specific activity and lower pH optimum than its "typical' counterpart (isoenzyme beta 1 beta 1) from the beta 1-chain predominant in Caucasians. Peptides were prepared by trypsin or CNBr cleavage, and were purified by exclusion chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). Structural analysis of the peptides showed that beta 2-Bern differs at one position from beta 1. Thus, Arg-47 in beta 1 is substituted by His in beta 2-Bern. This exchange, compatible with a one-base mutation, explains all functional differences by altered interactions with the pyrophosphate moiety of the coenzyme. The difference is also structurally identical to that found for another atypical beta 2-subunit, the beta 2-Oriental type of major Asian occurrence, linking these two atypical forms of human alcohol dehydrogenase. |
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Keywords: | DABTH-amino acid Reversed-phase high performance liquid chromatography (HPLC) Isocratic separation Quantitative determination |
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