Source:http://linkedlifedata.com/resource/pubmed/id/16300411
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
47
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pubmed:dateCreated |
2005-11-22
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pubmed:abstractText |
Elafin and its precursor trappin-2 (also called pre-elafin) are potent protein inhibitors of neutrophil serine proteases such as leukocyte elastase and proteinase 3. Trappin-2 has unique conserved sequence motifs rich in Gln and Lys residues. These motifs are substrates for transglutaminases that may enable trappin-2 to be cross-linked to extracellular matrix proteins, thus anchoring the inhibitor at its site of action. We have used Western blotting and ELISA-based assays to demonstrate that both elafin and trappin-2 can be conjugated to various extracellular matrix proteins in vitro by a type 2 transglutaminase. Cross-linked elafin and trappin-2 still inhibited their target proteases. Surface plasmon resonance studies allowed the determination of the kinetic constants governing the interaction of fibronectin-bound elafin and trappin-2 with neutrophil elastase and proteinase 3. Both inhibitors were potent inhibitors when cross-linked to fibronectin by transglutamination, with equilibrium dissociation constants K(i) for their interaction with target proteases of 0.3 nM (elastase-elafin), 20 nM (proteinase 3-elafin), 0.3 nM (elastase-trappin-2), and 12 nM (proteinase 3-trappin-2). The conjugated inhibitors reacted more slowly with their target enzymes than did the soluble inhibitors, perhaps due to their immobilization, with association rate constants of 2-7 x 10(5) M(-)(1) s(-)(1) for elastase and 1-4 x 10(4) M(-)(1) s(-)(1) for proteinase 3. We believe this is the first demonstration that transglutaminase-mediated cross-linking of serine protease inhibitors to proteins preserves their inhibitory capacities.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Elafin,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Leukocyte Elastase,
http://linkedlifedata.com/resource/pubmed/chemical/Myeloblastin,
http://linkedlifedata.com/resource/pubmed/chemical/PI3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Proteinase Inhibitory Proteins...,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Transglutaminases,
http://linkedlifedata.com/resource/pubmed/chemical/transglutaminase 2
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
29
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15610-8
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16300411-Elafin,
pubmed-meshheading:16300411-Extracellular Matrix Proteins,
pubmed-meshheading:16300411-Fibronectins,
pubmed-meshheading:16300411-GTP-Binding Proteins,
pubmed-meshheading:16300411-Humans,
pubmed-meshheading:16300411-Kinetics,
pubmed-meshheading:16300411-Leukocyte Elastase,
pubmed-meshheading:16300411-Myeloblastin,
pubmed-meshheading:16300411-Protein Interaction Mapping,
pubmed-meshheading:16300411-Protein Precursors,
pubmed-meshheading:16300411-Proteinase Inhibitory Proteins, Secretory,
pubmed-meshheading:16300411-Proteins,
pubmed-meshheading:16300411-Serine Endopeptidases,
pubmed-meshheading:16300411-Serine Proteinase Inhibitors,
pubmed-meshheading:16300411-Surface Plasmon Resonance,
pubmed-meshheading:16300411-Transglutaminases
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pubmed:year |
2005
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pubmed:articleTitle |
Elafin and its precursor trappin-2 still inhibit neutrophil serine proteinases when they are covalently bound to extracellular matrix proteins by tissue transglutaminase.
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pubmed:affiliation |
INSERM U618 Protéases et Vectorisation Pulmonaires and IFR 135 Imagerie Fonctionnelle, Université François Rabelais, 10 Bd Tonnellé, BP 3223, 37032 Tours Cedex, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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