32SC
CRYSTAL STRUCTURE OF BRD4-BD1 IN COMPLEX WITH COMPOUND 8
This is a non-PDB format compatible entry.
Summary for 32SC
| Entry DOI | 10.2210/pdb32sc/pdb |
| Descriptor | Bromodomain-containing protein 4, 3-methyl-~{N}-(2-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine (3 entities in total) |
| Functional Keywords | bromodomain, inhibitor, transcription |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 15352.68 |
| Authors | |
| Primary citation | Beier, A.,Platzer, G.,Hofurthner, T.,Ptaszek, A.L.,Lichtenecker, R.J.,Geist, L.,Fuchs, J.E.,McConnell, D.B.,Mayer, M.,Konrat, R. Probing Protein-Ligand Methyl-pi Interaction Geometries through Chemical Shift Measurements of Selectively Labeled Methyl Groups. J Med Chem, 67:13187-13196, 2024 Cited by PubMed Abstract: Fragment-based drug design is heavily dependent on the optimization of initial low-affinity binders. Herein we introduce an approach that uses selective labeling of methyl groups in leucine and isoleucine side chains to directly probe methyl-π contacts, one of the most prominent forms of interaction between proteins and small molecules. Using simple NMR chemical shift perturbation experiments with selected BRD4-BD1 binders, we find good agreement with a commonly used model of the ring-current effect as well as the overall interaction geometries extracted from the Protein Data Bank. By combining both interaction geometries and chemical shift calculations as fit quality criteria, we can position dummy aromatic rings into an AlphaFold model of the protein of interest. The proposed method can therefore provide medicinal chemists with important information about binding geometries of small molecules in fast and iterative matter, even in the absence of high-resolution experimental structures. PubMed: 39069741DOI: 10.1039/b508541a PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.25 Å) |
Structure validation
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