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Structural basis of RGD-hirudin binding to thrombin: Tyr3 and five C-terminal residues are crucial for inhibiting thrombin activity

Overview of attention for article published in BMC Molecular and Cell Biology, December 2014
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Title
Structural basis of RGD-hirudin binding to thrombin: Tyr3 and five C-terminal residues are crucial for inhibiting thrombin activity
Published in
BMC Molecular and Cell Biology, December 2014
DOI 10.1186/s12900-014-0026-9
Pubmed ID
Authors

Yinong Huang, Yanling Zhang, Bing Zhao, Qiping Xu, Xiushi Zhou, Houyan Song, Min Yu, Wei Mo

Abstract

BackgroundHirudin is an anti-coagulation protein produced by the salivary glands of the medicinal leech Hirudomedicinalis. It is a powerful and specific thrombin inhibitor. The novel recombinant hirudin, RGD-hirudin, which contains an RGD motif, competitively inhibits the binding of fibrinogen to GPIIb/IIIa on platelets, thus inhibiting platelet aggregation while maintaining its anticoagulant activity.ResultsRecombinant RGD-hirudin and six mutant variants (Y3A, S50A, Q53A, D55A, E57A and I59A), designed based on molecular simulations, were expressed in Pichia pastoris. The proteins were refolded and purified to homogeneity as monomers by gel filtration and anion exchange chromatography. The anti-thrombin activity of the six mutants and RGD-hirudin was tested. Further, we evaluated the binding of the mutant variants and RGD-hirudin to thrombin using BIAcore surface plasmon resonance analysis (SPR). Kinetics and affinity constants showed that the KD values of all six mutant proteins were higher than that of RGD-hirudin.ConclusionsThese findings contribute to a novel understanding of the interaction between RGD-hirudin and thrombin.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 9%
Italy 1 4%
Unknown 20 87%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 35%
Researcher 2 9%
Student > Bachelor 2 9%
Lecturer 1 4%
Student > Doctoral Student 1 4%
Other 2 9%
Unknown 7 30%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 26%
Agricultural and Biological Sciences 5 22%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Computer Science 1 4%
Immunology and Microbiology 1 4%
Other 2 9%
Unknown 7 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 October 2015.
All research outputs
#16,721,208
of 25,373,627 outputs
Outputs from BMC Molecular and Cell Biology
#740
of 1,233 outputs
Outputs of similar age
#210,452
of 360,076 outputs
Outputs of similar age from BMC Molecular and Cell Biology
#9
of 15 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,233 research outputs from this source. They receive a mean Attention Score of 4.0. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 360,076 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one is in the 33rd percentile – i.e., 33% of its contemporaries scored the same or lower than it.