5M3A
Crystal structure of BRD4 BROMODOMAIN 1 IN COMPLEX WITH LIGAND 2
Summary for 5M3A
| Entry DOI | 10.2210/pdb5m3a/pdb |
| Descriptor | Bromodomain-containing protein 4, 1,2-ETHANEDIOL, 3-methyl-6-(1-methyl-5-phenoxy-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine, ... (4 entities in total) |
| Functional Keywords | bromodomain, brd4 bd1, epigenetic, histone reader, transcription |
| Biological source | Homo sapiens (Human) |
| Cellular location | Nucleus: O60885 |
| Total number of polymer chains | 1 |
| Total formula weight | 15529.84 |
| Authors | Kessler, D.,Mayer, M.,Engelhardt, H.,Wolkerstorfer, B.,Geist, L. (deposition date: 2016-10-14, release date: 2017-09-27, Last modification date: 2024-01-17) |
| Primary citation | Geist, L.,Mayer, M.,Cockcroft, X.L.,Wolkerstorfer, B.,Kessler, D.,Engelhardt, H.,McConnell, D.B.,Konrat, R. Direct NMR Probing of Hydration Shells of Protein Ligand Interfaces and Its Application to Drug Design. J. Med. Chem., 60:8708-8715, 2017 Cited by PubMed Abstract: Fragment-based drug design exploits initial screening of low molecular weight compounds and their concomitant affinity improvement. The multitude of possible chemical modifications highlights the necessity to obtain structural information about the binding mode of a fragment. Herein we describe a novel NMR methodology (LOGSY titration) that allows the determination of binding modes of low affinity binders in the protein-ligand interface and reveals suitable ligand positions for the addition of functional groups that either address or substitute protein-bound water, information of utmost importance for drug design. The particular benefit of the methodology and in contrast to conventional ligand-based methods is the independence of the molecular weight of the protein under study. The validity of the novel approach is demonstrated on two ligands interacting with bromodomain 1 of bromodomain containing protein 4, a prominent cancer target in pharmaceutical industry. PubMed: 28910100DOI: 10.1021/acs.jmedchem.7b00845 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
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