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Mendeley readers
Attention Score in Context
| Title |
Direct and indirect mechanisms of KLK4 inhibition revealed by structure and dynamics
|
|---|---|
| Published in |
Scientific Reports, October 2016
|
| DOI | 10.1038/srep35385 |
| Pubmed ID | |
| Authors |
Blake T. Riley, Olga Ilyichova, Mauricio G. S. Costa, Benjamin T. Porebski, Simon J. de Veer, Joakim E. Swedberg, Itamar Kass, Jonathan M. Harris, David E. Hoke, Ashley M. Buckle |
| Abstract |
The kallikrein-related peptidase (KLK) family of proteases is involved in many aspects of human health and disease. One member of this family, KLK4, has been implicated in cancer development and metastasis. Understanding mechanisms of inactivation are critical to developing selective KLK4 inhibitors. We have determined the X-ray crystal structures of KLK4 in complex with both sunflower trypsin inhibitor-1 (SFTI-1) and a rationally designed SFTI-1 derivative to atomic (~1 Å) resolution, as well as with bound nickel. These structures offer a structural rationalization for the potency and selectivity of these inhibitors, and together with MD simulation and computational analysis, reveal a dynamic pathway between the metal binding exosite and the active site, providing key details of a previously proposed allosteric mode of inhibition. Collectively, this work provides insight into both direct and indirect mechanisms of inhibition for KLK4 that have broad implications for the enzymology of the serine protease superfamily, and may potentially be exploited for the design of therapeutic inhibitors. |
Mendeley readers
The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 34 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 11 | 32% |
| Researcher | 9 | 26% |
| Student > Doctoral Student | 3 | 9% |
| Student > Bachelor | 3 | 9% |
| Student > Master | 1 | 3% |
| Other | 3 | 9% |
| Unknown | 4 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 10 | 29% |
| Chemistry | 8 | 24% |
| Agricultural and Biological Sciences | 4 | 12% |
| Medicine and Dentistry | 3 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 4 | 12% |
| Unknown | 4 | 12% |
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 21 October 2016.
All research outputs
#20,346,264
of 22,893,031 outputs
Outputs from Scientific Reports
#105,728
of 123,706 outputs
Outputs of similar age
#273,561
of 316,323 outputs
Outputs of similar age from Scientific Reports
#3,126
of 3,640 outputs
Altmetric has tracked 22,893,031 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 123,706 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.2. This one is in the 1st percentile – i.e., 1% 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 316,323 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3,640 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.