Alpha1-antitrypsin: Structure, function and molecular biology of the gene

@article{Kalsheker1989Alpha1antitrypsinSF,
  title={Alpha1-antitrypsin: Structure, function and molecular biology of the gene},
  author={Noor A. Kalsheker},
  journal={Bioscience Reports},
  year={1989},
  volume={9},
  pages={129-138}
}
  • N. Kalsheker
  • Published 1 April 1989
  • Biology, Chemistry
  • Bioscience Reports
Alpha1-antitrypsin (AAT) deficiency is one of the commonest inherited disorders in white Caucasians. This association has provided major insights into the pathogenesis of chronic lung disease. The three dimensional structure of the protein and the structure of the gene have been determined. Some of the signals required for regulation of expression and tissue-specificity have been defined. Genetic manipulation of active site residues may provide a new generation of biological compounds with… 
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TLDR
The pleiomorphic nature of the gene has given rise to a variety of α1‐antitrypsin variants some of which are clinically important, which are providing interesting insights into the general processes of protein transport and intracellular protein degradation.
Structural characterization of recombinant alpha-1-antitrypsin expressed in a human cell line.
The design of a new truncated and engineered alpha1-antitrypsin based on theoretical studies: an antiprotease therapeutics for pulmonary diseases
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Although, the α1AT2 construct has the highest inhibitory activity even more that the native construct (α1AT5), results indicated the presence of protease inhibitory function of all the proteins' construct against elastase.
Development of anti-inflammatory peptidomimetics based on the structure of human alpha1-antitrypsin.
Immunochemical and functional properties of biliary alpha-1-antitrypsin.
TLDR
Biliary AAT was showed to have specific properties that differ from serum AAT regarding immunoreactivity, heat stability and antiproteolytical activity, and may be consistent with a conformational transition of the serpin molecule induced by the hydrophobic environment.
Recombinant production of native human α-1-antitrypsin protein in the liver HepG2 cells
TLDR
RecA1AT production in HepG2 cells grown under serum free condition at a large scale could provide a reliable source of the native protein suitable for therapeutic use in human.
Human kallikrein 4: enzymatic activity, inhibition, and degradation of extracellular matrix proteins
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The cleavage of extracellular matrix proteins by hK4 suggests that this enzyme may play a role in tissue remodeling and cancer metastasis.
Investigating the Regulation of Indole-3-Acetic Acid Production By the Plant Associated Microbe Pantoea sp. YR343
TLDR
Investigations have revealed a novel compound that specifically inhibits the formation of Z-1AT polymers, as well as in vitro and in silico strategies for identifying small molecules for treatment of  1ATD.
Point Mutation of a Non-Elastase-Binding Site in Human α1-Antitrypsin Alters Its Anti-Inflammatory Properties
TLDR
The data suggest that the anti-inflammatory profile of hAAT extends beyond direct RCL regions, and might be relevant for the elaboration ofhAAT formulations, as well as hA AT-based drugs, with enhanced anti- inflammatory attributes.
Identification of serpins specific for activated protein C using a lysate-based screening assay
TLDR
Site-specific random mutagenesis at the P2 and P1′ positions is conducted to determine if improvements could be made in the rate of APC inhibition, and it is found that Arg and Gln also confer specificity for APC.
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References

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Structure and variation of human α1–antitrypsin
TLDR
The sequence of α1–antitrypsin is in keeping with its role as a tissue scavenger of leukocyte elastase and helps explain why cigarette smoking greatly accelerates the onset and severity of this degenerative process to give the disease emphysema.
The amino acid substitutions of human α1‐antitrypsin M3, X and Z
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…
Synthesis in E. coli of α1-antitrypsin variants of therapeutic potential for emphysema and thrombosis
TLDR
The characterization of two α1-AT analogues produced in Escherichia coli are described, one of which is not only fully active as an elastase inhibitor but is also resistant to oxidative inactivation.
Plakalbumin, α1-antitrypsin, antithrombin and the mechanism of inflammatory thrombosis
TLDR
The demonstration here of the cleavage of antithrombin, by leukocyte elastase, explains an observed change in blood coagulation that accompanies severe inflammation and which can result in fatal thrombosis.
Assignment of the alpha 1-antitrypsin gene and a sequence-related gene to human chromosome 14 by molecular hybridization.
TLDR
Using a series of human-Chinese hamster somatic cell hybrids containing unique combinations of human chromosomes, the alpha 1-antitrypsin gene as well as the sequence-related gene have been assigned to human chromosome 14 by Southern hybridization and synteny analysis.
DNA polymorphisms of the human alpha 1 antitrypsin gene in normal subjects and in patients with pulmonary emphysema.
TLDR
The most frequent polymorphisms have been detected with the enzymes MspI, PstI, and TaqI at frequencies of 46.8%, 6.4%, and 5.0% respectively in the group of normal subjects.
Sequence homology and structural comparison between the chromosomal human α1-antitrypsin and chicken ovalbumin genes
TLDR
Human α1-antitrypsin and chicken ovalbumin show significant sequence homology and belong to a common protein super-family, yet the number, position and size of intervening sequences reveal that the two genes are dissimilar.
Deoxyribonucleic acid (DNA) polymorphism of the alpha 1-antitrypsin gene in chronic lung disease.
TLDR
The polymorphism identified in this study may be a new marker for genetic predisposition to chronic lung disease and a lack of association with any specific alpha 1-antitrypsin protein phenotype is indicated.
Species- and tissue-specific expression of human alpha 1-antitrypsin in transgenic mice.
TLDR
The presence of transcripts in other tissues indicates that the human pattern of expression is maintained, whereas the temporal activity of the introduced gene parallels that of the endogenous one during mouse embryogenesis.
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