2d26
From Proteopedia
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Active site distortion is sufficient for proteinase inhibit second crystal structure of covalent serpin-proteinase complex
Contents |
Overview
We report here the x-ray structure of a covalent serpin-proteinase complex, alpha1-proteinase inhibitor (alpha1PI) with porcine pancreatic elastase (PPE), which differs from the only other x-ray structure of such a complex, that of alpha1PI with trypsin, in showing nearly complete definition of the proteinase. alpha1PI complexes with trypsin, PPE, and human neutrophil elastase (HNE) showed similar rates of deacylation and enhanced susceptibility to proteolysis by exogenous proteinases in solution. The differences between the two x-ray structures therefore cannot arise from intrinsic differences in the inhibition mechanism. However, self-proteolysis of purified complex resulted in rapid cleavage of the trypsin complex, slower cleavage of the PPE complex, and only minimal cleavage of the HNE complex. This suggests that the earlier alpha1 PI-trypsin complex may have been proteolyzed and that the present structure is more likely to be representative of serpin-proteinase complexes. The present structure shows that active site distortion alone is sufficient for inhibition and suggests that enhanced proteolysis is not necessarily exploited in vivo.
Disease
Known diseases associated with this structure: Emphysema OMIM:[107400], Emphysema-cirrhosis OMIM:[107400], Hemorrhagic diathesis due to antithrombin Pittsburgh OMIM:[107400], Pulmonary disease, chronic obstructive, susceptibility to OMIM:[107400]
About this Structure
2D26 is a Protein complex structure of sequences from Homo sapiens and Sus scrofa. Active as Pancreatic elastase, with EC number 3.4.21.36 Full crystallographic information is available from OCA.
Reference
Active site distortion is sufficient for proteinase inhibition by serpins: structure of the covalent complex of alpha1-proteinase inhibitor with porcine pancreatic elastase., Dementiev A, Dobo J, Gettins PG, J Biol Chem. 2006 Feb 10;281(6):3452-7. Epub 2005 Dec 1. PMID:16321984
Page seeded by OCA on Thu Feb 21 16:54:36 2008
