Mechanisms contributing to the conformational and functional flexibility of plasminogen activator inhibitor-1.
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Aertgeerts K, De Bondt HL, De Ranter CJ, Declerck PJ
Mechanisms contributing to the conformational and functional flexibility of plasminogen activator inhibitor-1.
Nat Struct Biol. 1995 Oct;2(10):891-7.
- PubMed ID
- 7552714 [ View in PubMed]
- Abstract
Plasminogen activator inhibitor-1 (PAI-1) is unique among the serine proteinase inhibitors (serpins) in that it can adopt at least three different conformations (active, substrate and latent). We report the X-ray structure of a cleaved substrate variant of human PAI-1, which has a new beta-strand s4A formed by insertion of the amino-terminal portion of the reactive-site loop into beta-sheet A subsequent to cleavage. This is in contrast to the previous suggestion that the non-inhibitory function of substrate-type serpins is mainly due to an inability of the reactive-site loop to adopt this conformation. Comparison with the structure of latent PAI-1 provides insights into the molecular determinants responsible for the transition of the stressed active conformation to the thermostable latent conformation.