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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References
SHOWING 1-10 OF 56 REFERENCES
Basis of the Defect in α-1-Antitrypsin Deficiency
- Biology, MedicineNature
- 1973
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
- Biology
- 1975
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.
- BiologyAmerican journal of human genetics
- 1977
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.
- Medicine
- 1975
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.
- Medicine, BiologyJournal of clinical pathology
- 1977
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.
- Medicine, BiologyThe Journal of clinical investigation
- 1981
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.
Rat α1‐Antitrypsin. Preliminary characterisation of the in vitro mRNA translation product
- Biology
- 1981
Molecular abnormality of human alpha1-antitrypsin variant (Pi-ZZ) associated with plasma activity deficiency.
- BiologyProceedings of the National Academy of Sciences of the United States of America
- 1976
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…