| Title |
Deamidated Human Triosephosphate Isomerase is a Promising Druggable Target
|
|---|---|
| Published in |
Biomolecules, July 2020
|
| DOI | 10.3390/biom10071050 |
| Pubmed ID | |
| Authors |
Sergio Enríquez-Flores, Luis Antonio Flores-López, Itzhel García-Torres, Ignacio de la Mora-de la Mora, Nallely Cabrera, Pedro Gutiérrez-Castrellón, Yoalli Martínez-Pérez, Gabriel López-Velázquez |
| Abstract |
Therapeutic strategies for the treatment of any severe disease are based on the discovery and validation of druggable targets. The human genome encodes only 600-1500 targets for small-molecule drugs, but posttranslational modifications lead to a considerably larger druggable proteome. The spontaneous conversion of asparagine (Asn) residues to aspartic acid or isoaspartic acid is a frequent modification in proteins as part of the process called deamidation. Triosephosphate isomerase (TIM) is a glycolytic enzyme whose deamidation has been thoroughly studied, but the prospects of exploiting this phenomenon for drug design remain poorly understood. The purpose of this study is to demonstrate the properties of deamidated human TIM (HsTIM) as a selective molecular target. Using in silico prediction, in vitro analyses, and a bacterial model lacking the tim gene, this study analyzed the structural and functional differences between deamidated and nondeamidated HsTIM, which account for the efficacy of this protein as a druggable target. The highly increased permeability and loss of noncovalent interactions of deamidated TIM were found to play a central role in the process of selective enzyme inactivation and methylglyoxal production. This study elucidates the properties of deamidated HsTIM regarding its selective inhibition by thiol-reactive drugs and how these drugs can contribute to the development of cell-specific therapeutic strategies for a variety of diseases, such as COVID-19 and cancer. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 52 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 9 | 17% |
| Student > Master | 8 | 15% |
| Other | 6 | 12% |
| Student > Bachelor | 6 | 12% |
| Student > Ph. D. Student | 4 | 8% |
| Other | 8 | 15% |
| Unknown | 11 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 17 | 33% |
| Biochemistry, Genetics and Molecular Biology | 7 | 13% |
| Nursing and Health Professions | 3 | 6% |
| Psychology | 2 | 4% |
| Neuroscience | 2 | 4% |
| Other | 9 | 17% |
| Unknown | 12 | 23% |
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 31 July 2020.
All research outputs
#14,490,007
of 23,221,875 outputs
Outputs from Biomolecules
#1,849
of 4,299 outputs
Outputs of similar age
#221,050
of 396,895 outputs
Outputs of similar age from Biomolecules
#111
of 255 outputs
Altmetric has tracked 23,221,875 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,299 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has gotten more attention than average, scoring higher than 53% of its peers.
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 396,895 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 255 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.