Inhibitory conformation of the reactive loop of α1-antitrypsin
| Autor: | Robin W. Carrell, David A. Lomas, Peter R. Elliott, Jan Pieter Abrahams |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Liver Cirrhosis
Models Molecular Polymers Protein Conformation Biology Serpin Crystallography X-Ray medicine.disease_cause Structure-Activity Relationship Protein structure Structural Biology Neuroserpin medicine Humans Structure–activity relationship Familial encephalopathy with neuroserpin inclusion bodies Molecular Biology Mutation Heparin Antithrombin medicine.disease Biochemistry alpha 1-Antitrypsin Serine Proteinase Inhibitors medicine.drug |
| Zdroj: | Nature Structural & Molecular Biology. 3:676-681 |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | The reactive site loop of the serpin family of serine proteinase inhibitors is flexible and can adopt a number of diverse conformations. A 2.9 A resolution structure of alpha 1-antitrypsin-the principal proteinase inhibitor in human plasma-shows the loop in a stable canonical conformation matching that found in all other families of serine proteinase inhibitors. This unexpected finding in the absence of loop insertion into the body of the molecule favours a two-stage mechanism of inhibition and provides a model for the heparin activation of antithrombin. The beta-pleated strand conformation of the loop also accounts for the polymerization of the serpins in disease and for their association with other beta-sheet structures, most notably the beta-amyloid of Alzheimer's disease. |
| Databáze: | OpenAIRE |
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