期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1986
卷号：83
期号：3
页码：634-638
DOI：10.1073/pnas.83.3.634
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Class I human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1 ) consists of several homo- and heterodimers of alpha, beta, and gamma subunits that are governed by the ADH1, ADH2, and ADH3 loci. We previously cloned a full length of cDNA for the beta subunit, and the complete sequence of 374 amino acid residues was established. cDNAs for the alpha and gamma subunits were cloned and characterized. A human liver cDNA library, constructed in phage lambda gt11, was screened by using a synthetic oligonucleotide probe that was matched to the gamma but not to the beta sequence. Clone pUCADH gamma 21 and clone pUCADH alpha 15L differed from beta cDNA with respect to restriction sites and hybridization with the nucleotide probe. Clone pUCADH gamma 21 contained an insertion of 1.5 kilobase pairs (kbp) and encodes 374 amino acid residues compatible with the reported amino acid sequence of the gamma subunit. Clone pUCADH alpha 15L contained an insertion of 2.4 kbp and included nucleotide sequences that encode 374 amino acid residues for another subunit, the alpha subunit. In addition, this clone contained the sequences that encode the COOH-terminal part of the beta subunit at its extended 5' region. The amino acid sequences and coding regions of the cDNAs of the three subunits are very similar (approximately 93-95% identity). A high degree of resemblance is observed also in their 3' noncoding regions. However, distinctive differences exist in the vicinity of the Zn-binding cysteine residue at position 46--i.e., Cys-Gly-Thr in the alpha, Cys-Arg-Thr in the wild-type beta 1, Cys-His-Thr in the Oriental-type beta 2, and Cys-Arg-Ser in the gamma, reflecting the differences in their kinetic properties. Based on the cDNA sequences and the deduced amino acid sequences of the three subunits, their structural and evolutionary relationships are discussed.
