Microsecond timescale conformational dynamics of a small‐molecule ligand within the active site of a protein
| dc.contributor.author | Kotschy, Julia | |
| dc.contributor.author | Söldner, Benedikt | |
| dc.contributor.author | Singh, Himanshu | |
| dc.contributor.author | Vasa, Suresh K. | |
| dc.contributor.author | Linser, Rasmus | |
| dc.date.accessioned | 2025-03-20T08:29:06Z | |
| dc.date.available | 2025-03-20T08:29:06Z | |
| dc.date.issued | 2023-11-16 | |
| dc.description.abstract | The possible internal dynamics of non-isotope-labeled small-molecule ligands inside a target protein is inherently difficult to capture. Whereas high crystallographic temperature factors can denote either static disorder or motion, even moieties with very low B-factors can be subject to vivid motion between symmetry-related sites. Here we report the experimental identification of internal μs timescale dynamics of a high-affinity, natural-abundance ligand tightly bound to the enzyme human carbonic anhydrase II (hCAII) even within a crystalline lattice. The rotamer jumps of the ligand's benzene group manifest themselves both, in solution and fast magic-angle spinning solid-state NMR 1H R1ρ relaxation dispersion, for which we obtain further mechanistic insights from molecular-dynamics (MD) simulations. The experimental confirmation of rotameric jumps in bound ligands within proteins in solution or the crystalline state may improve understanding of host-guest interactions in biology and supra-molecular chemistry and may facilitate medicinal chemistry for future drug campaigns. | en |
| dc.identifier.uri | http://hdl.handle.net/2003/43558 | |
| dc.identifier.uri | http://dx.doi.org/10.17877/DE290R-25391 | |
| dc.language.iso | en | |
| dc.relation.ispartofseries | Angewandte Chemie / International edition; 63(5) | |
| dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject | Ligand entropy | en |
| dc.subject | Protein complexes | en |
| dc.subject | Protein dynamics | en |
| dc.subject | Proton detection | en |
| dc.subject | Solid-state NMR | en |
| dc.subject.ddc | 540 | |
| dc.title | Microsecond timescale conformational dynamics of a small‐molecule ligand within the active site of a protein | en |
| dc.type | Text | |
| dc.type.publicationtype | Article | |
| dcterms.accessRights | open access | |
| eldorado.secondarypublication | true | |
| eldorado.secondarypublication.primarycitation | J. Kotschy, B. Söldner, H. Singh, S. K. Vasa, R. Linser, Angew. Chem. Int. Ed. 2024, 63, e202313947. https://doi.org/10.1002/anie.202313947 | |
| eldorado.secondarypublication.primaryidentifier | https://doi.org/10.1002/anie.202313947 |
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