α(1)-Antitrypsin and the serpins: variation and countervariation

α(1)-Antitrypsin is a plasma protein which protects elastic tissue from proteolytic attack. Consequently, genetic deficiency, or the oxidation of its reactive centre in cigarette smokers can result in the degenerative lung disease emphysema. Structural studies explain the mechanisms involved and have also drawn attention to a new family of serine proteinase inhibitors. The specificity of each of these inhibitors is primarily dependent on a single amino acid at its reactive centre. Site-directed mutagenesis is enabling the production of specifically designed inhibitors for therapeutic use, including an improved replacement for α(1)-antitrypsin deficiency.