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Protein Sci. 2000 Feb;9(2):417-20.

Cleaved antitrypsin polymers at atomic resolution.

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  • 1The Ian Potter Foundation Protein Crystallography Laboratory, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.


Alpha1-antitrypsin deficiency, which can lead to both emphysema and liver disease, is a result of the accumulation of alpha1-antitrypsin polymers within the hepatocyte. A wealth of biochemical and biophysical data suggests that alpha1-antitrypsin polymers form via insertion of residues from the reactive center loop of one molecule into the beta-sheet of another. However, this long-standing hypothesis has not been confirmed by direct structural evidence. Here, we describe the first crystallographic evidence of a beta-strand linked polymer form of alpha1-antitrypsin: the crystal structure of a cleaved alpha1-antitrypsin polymer.

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