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rdf:type |
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lifeskim:mentions |
umls-concept:C0014139,
umls-concept:C0015576,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0023621,
umls-concept:C0030190,
umls-concept:C0030956,
umls-concept:C0205409,
umls-concept:C0597357,
umls-concept:C1167622,
umls-concept:C1519025
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pubmed:issue |
3
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pubmed:dateCreated |
2006-10-12
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pubmed:abstractText |
The functions of the serpin PAI-1 (plasminogen activator inhibitor-1) are based on molecular interactions with its target proteases uPA and tPA (urokinase-type and tissue-type plasminogen activator respectively), with vitronectin and with endocytosis receptors of the low-density-lipoprotein family. Understanding the significance of these interactions would be facilitated by the ability to block them individually. Using phage display, we have identified the disulfide-constrained peptide motif CFGWC with affinity for natural human PAI-1. The three-dimensional structure of a peptide containing this motif (DVPCFGWCQDA) was determined by liquid-state NMR spectroscopy. A binding site in the so-called flexible joint region of PAI-1 was suggested by molecular modelling and validated through binding studies with various competitors and site-directed mutagenesis of PAI-1. The peptide with an N-terminal biotin inhibited the binding of the uPA-PAI-1 complex to the endocytosis receptors low-density-lipoprotein-receptor-related protein 1A (LRP-1A) and very-low-density-lipoprotein receptor (VLDLR) in vitro and inhibited endocytosis of the uPA-PAI-1 complex in U937 cells. We conclude that the isolated peptide represents a novel approach to pharmacological interference with the functions of PAI-1 based on inhibition of one specific molecular interaction.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-10085143,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-10913251,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-10933492,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-11057674,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-11179976,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-11278457,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-11733024,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-12067733,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-12074887,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-12123794,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-12475206,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-12656676,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-12694180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-12694181,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-12723974,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-1375944,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-1731226,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-1920436,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-1966892,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-2690952,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-3098860,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-3520936,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-7621813,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-7664984,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-7682645,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-7760743,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-8373822,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-8520220,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-8578527,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-9405275,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-9477948,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-9497365,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-9572853,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-9716154,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-9757107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16813566-9843178
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cystine,
http://linkedlifedata.com/resource/pubmed/chemical/Low Density Lipoprotein...,
http://linkedlifedata.com/resource/pubmed/chemical/Micelles,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Library,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/SERPINE1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator,
http://linkedlifedata.com/resource/pubmed/chemical/VLDL receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1470-8728
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
399
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
387-96
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
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