Structure and variation of human α1–antitrypsin

@article{Carrell1982StructureAV,
  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},
  journal={Nature},
  year={1982},
  volume={298},
  pages={329-334}
}
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. 
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The disease spectrum is discussed (including emphysema, liver, and vasculitic diseases) and the variable clinical expression of the deficiency state is focused on.
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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
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References

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TLDR
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
TLDR
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.
TLDR
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.
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TLDR
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.
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TLDR
It is considered probable that heterozygous (PiMZ) alpha 1-antitrypsin deficiency is associated with an increased incidence of cirrhosis, hepatic fibrosis, and hepatocellular carcinoma.
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TLDR
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
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