| Title |
Mapping the dynamics of ligand reorganization via 13CH3 and 13CH2 relaxation dispersion at natural abundance
|
|---|---|
| Published in |
Journal of Biomolecular NMR, July 2009
|
| DOI | 10.1007/s10858-009-9349-4 |
| Pubmed ID | |
| Authors |
Jeffrey W. Peng, Brian D. Wilson, Andrew T. Namanja |
| Abstract |
Flexible ligands pose challenges to standard structure-activity studies since they frequently reorganize their conformations upon protein binding and catalysis. Here, we demonstrate the utility of side chain (13)C relaxation dispersion measurements to identify and quantify the conformational dynamics that drive this reorganization. The dispersion measurements probe methylene (13)CH(2) and methyl (13)CH(3) groups; the latter are highly prevalent side chain moieties in known drugs. Combining these side chain studies with existing backbone dispersion studies enables a comprehensive investigation of mus-ms conformational dynamics related to binding and catalysis. We perform these measurements at natural (13)C abundance, in congruence with common pharmaceutical research settings. We illustrate these methods through a study of the interaction of a phosphopeptide ligand with the peptidyl-prolyl isomerase, Pin1. The results illuminate the side-chain moieties that undergo conformational readjustments upon complex formation. In particular, we find evidence that multiple exchange processes influence the side chain dispersion profiles. Collectively, our studies illustrate how side-chain relaxation dispersion can shed light on ligand conformational transitions required for activity, and thereby suggest strategies for its optimization. |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 4% |
| France | 1 | 4% |
| Unknown | 22 | 92% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 8 | 33% |
| Researcher | 6 | 25% |
| Professor | 2 | 8% |
| Lecturer | 2 | 8% |
| Student > Master | 1 | 4% |
| Other | 3 | 13% |
| Unknown | 2 | 8% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 12 | 50% |
| Agricultural and Biological Sciences | 5 | 21% |
| Biochemistry, Genetics and Molecular Biology | 3 | 13% |
| Medicine and Dentistry | 1 | 4% |
| Unknown | 3 | 13% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. 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 11 August 2009.
All research outputs
#5,563,524
of 22,705,019 outputs
Outputs from Journal of Biomolecular NMR
#82
of 614 outputs
Outputs of similar age
#29,563
of 110,416 outputs
Outputs of similar age from Journal of Biomolecular NMR
#5
of 12 outputs
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So far Altmetric has tracked 614 research outputs from this source. They receive a mean Attention Score of 2.9. This one has done well, scoring higher than 86% of its peers.
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We're also able to compare this research output to 12 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 50% of its contemporaries.