Alpha 1-antitrypsin deficiency. A conformational disease.
The serpin family of protease inhibitors, to which alpha 1-antitrypsin belongs, has the unique feature of a mobile reactive center. Mutations within the critical regions of the molecule that control this mobility can allow premature changes in conformation with consequent abnormalities in folding and accompanying polymer formation. These abnormalities explain the plasma deficiency and liver inclusions associated with the common Z variant, as well as other variants of alpha 1-antitrypsin. The understanding of the molecular mechanisms provides a satisfying explanation for the clinical findings associated with these deficiency variants.
Carrell
R W
RW
Department of Haematology, University of Cambridge, England, UK.
Lomas
D A
DA
Sidhar
S
S
Foreman
R
R
D006801:Humans; D008107:Liver Diseases / Q000378:metabolism / Q000503:physiopathology; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D011108:Polymers; D011487:Protein Conformation; D015843:Serpins / Q000737:chemistry; D013329:Structure-Activity Relationship; D000515:alpha 1-Antitrypsin / Q000737:chemistry*; D019896:alpha 1-Antitrypsin Deficiency
D011108:Polymers; D015843:Serpins; D000515:alpha 1-Antitrypsin