Medium- and short-chain dehydrogenase/reductase gene and protein families The role of zinc for alcohol dehydrogenase structure and function

• Published in: Cellular and molecular life sciences : CMLS Vol. 65; no. 24; pp. 3961 - 3970
• Main Authors: Auld, D. S., Bergman, T.
• Format: Journal Article
• Language: English
• Published: Basel Birkhäuser-Verlag 01.12.2008; Springer Nature B.V
• Subjects: Alcohol Dehydrogenase - chemistry; Alcohol Dehydrogenase - metabolism; Amino Acid Sequence; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Catalysis; Catalytic Domain; Cell Biology; Enzymes; Genes; Humans; Life Sciences; Medicin och hälsovetenskap; Molecular biology; Molecular Sequence Data; Multi-author Review; Multigene Family; Peptides - chemistry; Peptides - metabolism; Proteins; Zinc; Zinc - metabolism; structural zinc site; Alcohol dehydrogenase; zinc; entatic state; metalloenzymes; catalytic zinc site
• ISSN: 1420-682X; 1420-9071; 1420-9071
• DOI: 10.1007/s00018-008-8593-1

. Zinc plays an important role in the structure and function of many enzymes, including alcohol dehydrogenases (ADHs) of the MDR type (mediumchain dehydrogenases/reductases). Active site zinc participates in catalytic events, and structural site zinc maintains structural stability. MDR-types of ADHs have both of these zinc sites but with some variation in ligands and spacing. The catalytic zinc sites involve three residues with different spacings from two separate protein segments, while the structural zinc sites involve four residues and cover a local segment of the protein chain (Cys97-Cys111 in horse liver class I ADH). This review summarizes properties of both ADH zinc sites, and relates them to zinc sites of proteins in general. In addition, it highlights a separate study of zinc binding peptide variants of the horse liver ADH structural zinc site. The results show that zinc coordination of the free peptide differs markedly from that of the enzyme (one His / three Cys versus four Cys), suggesting that the protein zinc site is in an energetically strained conformation relative to that of the peptide. This finding is a characteristic of an entatic state, implying a functional nature for this zinc site.