HD1, a Thrombin-directed Aptamer, Binds Exosite 1 on Prothrombin with High Affinity and Inhibits Its Activation by Prothrombinase *
Journal of Biological Chemistry, ISSN: 0021-9258, Vol: 281, Issue: 49, Page: 37477-37485
2006
- 63Citations
- 63Captures
- 1Mentions
Metric Options: Counts1 Year3 YearSelecting the 1-year or 3-year option will change the metrics count to percentiles, illustrating how an article or review compares to other articles or reviews within the selected time period in the same journal. Selecting the 1-year option compares the metrics against other articles/reviews that were also published in the same calendar year. Selecting the 3-year option compares the metrics against other articles/reviews that were also published in the same calendar year plus the two years prior.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations63
- Citation Indexes63
- 63
- CrossRef47
- Captures63
- Readers63
- 63
- Mentions1
- References1
- Wikipedia1
Article Description
Incorporation of prothrombin into the prothrombinase complex is essential for rapid thrombin generation at sites of vascular injury. Prothrombin binds directly to anionic phospholipid membrane surfaces where it interacts with the enzyme, factor Xa, and its cofactor, factor Va. We demonstrate that HD1, a thrombin-directed aptamer, binds prothrombin and thrombin with similar affinities ( Kd values of 86 and 34 n m, respectively) and attenuates prothrombin activation by prothrombinase by over 90% without altering the activation pathway. HD1-mediated inhibition of prothrombin activation by prothrombinase is factor Va-dependent because ( a ) the inhibitory activity of HD1 is lost if factor Va is omitted from the prothrombinase complex and ( b ) prothrombin binding to immobilized HD1 is reduced by factor Va. These data suggest that HD1 competes with factor Va for prothrombin binding. Kinetic analyses reveal that HD1 produces a 2-fold reduction in the k cat for prothrombin activation by prothrombinase and a 6-fold increase in the Km, highlighting the contribution of the factor Va-prothrombin interaction to prothrombin activation. As a high affinity, prothrombin exosite 1-directed ligand, HD1 inhibits prothrombin activation more efficiently than Hir 54–65 (SO - 3 ). These findings suggest that exosite 1 on prothrombin exists as a proexosite only for ligands whose primary target is thrombin rather than prothrombin.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0021925820719216; http://dx.doi.org/10.1074/jbc.m607359200; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33845988051&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/17046833; http://www.jbc.org/lookup/doi/10.1074/jbc.M607359200; https://syndication.highwire.org/content/doi/10.1074/jbc.M607359200; https://linkinghub.elsevier.com/retrieve/pii/S0021925820719216; https://dx.doi.org/10.1074/jbc.m607359200
American Society for Biochemistry & Molecular Biology (ASBMB)
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