Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
43
|
| pubmed:dateCreated |
1995-12-14
|
| pubmed:abstractText |
The distinguishing characteristic of vampire bat (Desmodus rotundus) salivary plasminogen activators (DSPAs) is their strict requirement for fibrin as a cofactor. DSPAs consist of structural modules known from urokinase (u-PA) and tissue-type plasminogen activator (t-PA) such as finger (F), epidermal growth factor (E), kringle (K), and protease (P), combining to four genetically and biochemically distinct isoenzymes, exhibiting the formulas FEKP (DSPA alpha 1 and alpha 2) and EKP and KP (DSPA beta and DSPA gamma). Only DSPA alpha 1 and alpha 2 bind to fibrin. All DSPAs are single-chain molecules, displaying substantial amidolytic activity. In a plasminogen activation assay, all four DSPAs are almost inactive in the absence of fibrin but strongly stimulated by fibrin addition. The catalytic efficiency (kcat/Km) of DSPA alpha 1 increases 10(5)-fold, whereas the corresponding value of t-PA is only 550. The ratio of the bimolecular rate constants of plasminogen activation in the presence of fibrin versus fibrinogen (fibrin selectivity) of DSPA alpha 1, alpha 2, beta, gamma, and t-PA was found to be 13,000, 6500, 250, 90, and 72, respectively. Whereas all DSPAs are therefore more fibrin dependent and fibrin selective than t-PA, the extent depends on the respective presence of the various domains. The introduction of a plasmin-sensitive cleavage site in a position akin to the one in t-PA partially obliterates fibrin cofactor requirement. Fibrin dependence and fibrin selectivity of DSPAs are accordingly mediated by fibrin binding, which involves the F domain, as yet undefined determinants within the K and P domains, and by the absence of a plasmin-sensitive activation site. These findings transcend the current understanding of fibrin-mediated stimulation of plasminogen activation: in addition to fibrin binding, specific protein-protein interactions come into play, which stabilize the enzyme in its active conformation.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/6-Aminocaproic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Fibrin,
http://linkedlifedata.com/resource/pubmed/chemical/Fibrinogen,
http://linkedlifedata.com/resource/pubmed/chemical/Fibrinolytic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Plasminogen Activator,
http://linkedlifedata.com/resource/pubmed/chemical/benzoyl-Ile-Glu-Gly-Arg-p-nitroanili...,
http://linkedlifedata.com/resource/pubmed/chemical/salivary plasminogen activator...
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
27
|
| pubmed:volume |
270
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
25596-603
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:7592732-6-Aminocaproic Acid,
pubmed-meshheading:7592732-Animals,
pubmed-meshheading:7592732-Base Sequence,
pubmed-meshheading:7592732-Chiroptera,
pubmed-meshheading:7592732-Enzyme Activation,
pubmed-meshheading:7592732-Fibrin,
pubmed-meshheading:7592732-Fibrinogen,
pubmed-meshheading:7592732-Fibrinolytic Agents,
pubmed-meshheading:7592732-Hydrolysis,
pubmed-meshheading:7592732-Isoenzymes,
pubmed-meshheading:7592732-Kinetics,
pubmed-meshheading:7592732-Molecular Sequence Data,
pubmed-meshheading:7592732-Oligopeptides,
pubmed-meshheading:7592732-Plasminogen,
pubmed-meshheading:7592732-Plasminogen Activators,
pubmed-meshheading:7592732-Protein Binding,
pubmed-meshheading:7592732-Recombinant Proteins,
pubmed-meshheading:7592732-Saliva,
pubmed-meshheading:7592732-Substrate Specificity,
pubmed-meshheading:7592732-Tissue Plasminogen Activator
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Structural features mediating fibrin selectivity of vampire bat plasminogen activators.
|
| pubmed:affiliation |
Research Laboratories, Schering AG Berlin, Federal Republic of Germany.
|
| pubmed:publicationType |
Journal Article,
Comparative Study
|