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Molecular abnormality of PI S variant of human alpha1-antitrypsin
Abstract:
Alpha1-antitrypsin variant protein was purified to homogeneity from a PI S-S subject with a mild deficiency of plasma trypsin inhibiting capacity. Molecular weight, specific trypsin inhibitory activity, and composition of amino acids and carbohydrates were similar to the proteins purified from Pi M-M individuals with normal alpha1-antitrypsin activity. The structural difference between the normal and the variant alpha1-antitrypsin was elucidated by peptide mapping of their tryptic digests. An amino acid substitution of glutamic acid in the normal protein to valine in the variant protein was found. The result is consistent with the previously reported amino acid substitution in Pi S-Christchurch.
Insights
Researchers purified alpha-1 antitrypsin (AAT) variant protein from a patient with mild AAT deficiency. Structural analysis revealed a specific amino acid substitution, explaining the variant
Area of Science:
- Biochemistry
- Genetics
- Proteomics
Background:
- Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder.
- The PI S-S phenotype is associated with mild AAT deficiency.
- Understanding AAT variants is crucial for diagnosing and managing deficiency.
Purpose of the Study:
- To purify and characterize the AAT variant protein from a PI S-S subject.
- To elucidate the structural differences between normal and variant AAT.
- To identify the specific amino acid substitution responsible for the variant.
Main Methods:
- Protein purification to homogeneity.
- Analysis of molecular weight, trypsin inhibitory activity, and composition.
- Peptide mapping of tryptic digests.
Main Results:
- Purified AAT variant protein showed similar molecular weight and activity to normal AAT.
- Peptide mapping identified a structural difference.
- The variant protein has a glutamic acid to valine substitution.
Conclusions:
- The identified amino acid substitution explains the structural difference in the AAT variant.
- This finding is consistent with previous reports on the Pi S-Christchurch variant.
- The study contributes to the understanding of AAT deficiency genetics and structure.