The role of zinc for alcohol dehydrogenase structure and function

被引:71
作者
Auld, D. S. [2 ]
Bergman, T. [1 ]
机构
[1] Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden
[2] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA
基金
瑞典研究理事会;
关键词
Alcohol dehydrogenase; zinc; metalloenzymes; catalytic zinc site; structural zinc site; entatic state;
D O I
10.1007/s00018-008-8593-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3961 / 3970
页数:10
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