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The design of a new truncated and engineered alpha1-antitrypsin based on theoretical studies: an antiprotease therapeutics for pulmonary diseases

Overview of attention for article published in Theoretical Biology and Medical Modelling, May 2013
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Title
The design of a new truncated and engineered alpha1-antitrypsin based on theoretical studies: an antiprotease therapeutics for pulmonary diseases
Published in
Theoretical Biology and Medical Modelling, May 2013
DOI 10.1186/1742-4682-10-36
Pubmed ID
Authors

Nazanin Pirooznia, Sadegh Hasannia, Seyed Shahriar Arab, Abbas Sahebghadam Lotfi, Mostafa Ghanei, Abbas Shali

Abstract

Alpha 1- antitrypsin (alpha1AT) a 54 kDa glycoprotein is a protease inhibitor. In the absence of alpha1AT, elastase released by lung macrophages, was not inhibited and lead to elastin breakdown and pulmonary problems such as emphysema or COPD. alpha1AT has three site of N-glycosylation and a characteristic reactive central loop (RCL). As small-scale medicines are preferred for pulmonary drug delivery, in this study alpha1ATs (1, 2, 3, 4 and 5) were engineered and shortened from the N-terminal region. In order to investigate the effect of different mutations and the deletion of 46 amino acids theoretical studies were performed. Homology modeling was performed to generate the 3D structure of alpha1ATs. The 10 ns Molecular Dynamic (MD) simulations were carried out to refine the models. Results from MD and protein docking showed that alpha1AT2 has the highest binding affinity for neutrophil elastase, provided the basis for the experimental phase in which sequences from the five alpha1AT constructs were inserted into the expression vector pGAPZalpha and expressed in the yeast Pichia pastoris. Although, the alpha1AT2 construct has the highest inhibitory activity even more that the native construct (alpha1AT5), results indicated the presence of protease inhibitory function of all the proteins' construct against elastase.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 5%
United States 1 5%
Australia 1 5%
Unknown 19 86%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 18%
Researcher 4 18%
Other 3 14%
Student > Doctoral Student 3 14%
Professor > Associate Professor 2 9%
Other 2 9%
Unknown 4 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 27%
Agricultural and Biological Sciences 4 18%
Medicine and Dentistry 3 14%
Immunology and Microbiology 1 5%
Mathematics 1 5%
Other 2 9%
Unknown 5 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 December 2013.
All research outputs
#11,132,561
of 12,516,972 outputs
Outputs from Theoretical Biology and Medical Modelling
#182
of 227 outputs
Outputs of similar age
#176,673
of 212,237 outputs
Outputs of similar age from Theoretical Biology and Medical Modelling
#22
of 38 outputs
Altmetric has tracked 12,516,972 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 227 research outputs from this source. They receive a mean Attention Score of 3.9. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 38 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.