Structure and variation of human α1–antitrypsin

  title={Structure and variation of human $\alpha$1–antitrypsin},
  author={Robin W. Carrell and Jan O. Jeppsson and Carl Bertil Laurell and Stephen O. Brennan and Maurice C. Owen and Lloyd Vaughan and D. R. Boswell},
The sequence of α1–antitrypsin is in keeping with its role as a tissue scavenger of leukocyte elastase. Two abnormal variants commonly present in Europeans cause a deficiency that predisposes them to a progressive loss of lung elasticity. The nature of the reactive centre helps explain why cigarette smoking greatly accelerates the onset and severity of this degenerative process to give the disease emphysema. 
α1-Antitrypsin deficiency • 4: Molecular pathophysiology
The molecular basis of α1-antitrypsin deficiency is reviewed and is shown to be due to the accumulation of mutant protein as ordered polymers within the endoplasmic reticulum of hepatocytes. The
Alpha 1-antitrypsin deficiency. A conformational disease.
The understanding of the molecular mechanisms provides a satisfying explanation for the clinical findings associated with these deficiency variants of alpha 1-antitrypsin.
Discovery ofα1-antitrypsin deficiency
The author reviews the early history ofα1-antitrypsin (AAT) deficiency; the biochemical characterization of this inborn error of metabolism, its pattern of inheritance, frequency and predisposition
Alpha1-antitrypsin: Structure, function and molecular biology of the gene
Genetic manipulation of active site residues may provide a new generation of biological compounds with potential therapeutic applications in AAT deficiency and other inherited disorders.
A 30-Year Perspective on α1-Antitrypsin Deficiency
The disease spectrum is discussed (including emphysema, liver, and vasculitic diseases) and the variable clinical expression of the deficiency state is focused on.
Alpha One Antitrypsin Deficiency: From Gene to Treatment
Clinical features of α1-antitrypsin deficiency, the genetic mutations known to cause it, and how they do so at a molecular level are reviewed and specific treatments for the disorder based on this knowledge will be reviewed.
α1-Antitrypsin Deficiency
α1-Antitrypsin (AAT), also referred to as α1-protease inhibitor, is the main antiprotease of human serum. It belongs to the class of proteins known as serpins (serine protease inhibitors). Because


Basis of the Defect in α-1-Antitrypsin Deficiency
The proportion of the variant form, and family studies, strongly support a single autosomal locus for α-1-antitrypsin.
Characterization of α1-Antitrypsin in the Inclusion Bodies from the Liver in α1-Antitrypsin Deficiency
The results strongly suggest an abnormal amino acid sequence in the peptide chain of the deficient antitrypsin and the interference with glycosylation may be related to steric hindrance.
Molecular abnormality of PI S variant of human alpha1-antitrypsin.
The structural difference between the normal and the variant alpha1-antitrypsin was elucidated by peptide mapping of their tryptic digests, and an amino acid substitution of glutamic acid in the normal protein to valine in the variant protein was found.
Alpha-1-antitrypsin deficiency in New Zealand.
A severe deficiency of the serum protein alpha-1-antitrypsin can be expected to occur in 1 in 750 European New Zealanders, and individuals at risk should be protected from respiratory irritants and liver toxins.
Alpha-1-antitrypsin bodies in the liver.
It is considered probable that heterozygous (PiMZ) alpha 1-antitrypsin deficiency is associated with an increased incidence of cirrhosis, hepatic fibrosis, and hepatocellular carcinoma.
Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema.
Lower respiratory tract of non-smoking individuals with normal serum antiproteases and individuals with PiZ homozygous alpha 1-antitrypsin deficiency underwent bronchoalveolar lavage to evaluate the antiprotease screen of their lower respiratory tract, suggesting their vulnerability to neutrophil elastase is always present.
Molecular abnormality of human alpha1-antitrypsin variant (Pi-ZZ) associated with plasma activity deficiency.
A human alpha1-antitrypsin variant protein was purified to homogeneity from homozygous variant subjects (Pi-ZZ) who had a deficiency of plasma trypsin inhibitory capacity. Molecular weight, specific