4.7 Article

The role of zinc for alcohol dehydrogenase structure and function

期刊

CELLULAR AND MOLECULAR LIFE SCIENCES
卷 65, 期 24, 页码 3961-3970

出版社

SPRINGER BASEL AG
DOI: 10.1007/s00018-008-8593-1

关键词

Alcohol dehydrogenase; zinc; metalloenzymes; catalytic zinc site; structural zinc site; entatic state

资金

  1. Swedish Research Council, the Swedish Cancer Society
  2. NIH [GM47534]
  3. Knut and Alice Wallenberg Foundation

向作者/读者索取更多资源

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.

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