8R1I
Human Carbonic Anhydrase II (hCAII) in complex with (R)-N-(3-Indol-1-yl-2-methyl-propyl)-4-sulfamoyl-benzamide
Summary for 8R1I
| Entry DOI | 10.2210/pdb8r1i/pdb |
| Descriptor | Carbonic anhydrase 2, (R)-N-(3-INDOL-1-YL-2-METHYL-PROPYL)-4-SULFAMOYL-BENZAMIDE, ZINC ION, ... (4 entities in total) |
| Functional Keywords | inhibitor, carbonic anhydrase, co-crystallization, complex, zn2+ coordination site, metal binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 30243.45 |
| Authors | Kotschy, J.,Gasper, R.,Linser, R. (deposition date: 2023-11-02, release date: 2023-12-06, Last modification date: 2024-01-31) |
| Primary citation | Kotschy, J.,Soldner, B.,Singh, H.,Vasa, S.K.,Linser, R. Microsecond Timescale Conformational Dynamics of a Small-Molecule Ligand within the Active Site of a Protein. Angew.Chem.Int.Ed.Engl., 63:e202313947-e202313947, 2024 Cited by PubMed 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 H R 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. PubMed: 37974542DOI: 10.1002/anie.202313947 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.46 Å) |
Structure validation
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