6xv3
CRYSTAL STRUCTURE OF BRD4-BD1 WITH COMPOUND 3
Structural highlights
DiseaseBRD4_HUMAN Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.[1] [2] FunctionBRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). Publication Abstract from PubMedWhile CH-pi-interactions with target proteins are crucial determinants for the affinity of arguably every drug molecule, no method exists to directly measure the strength of individual CH-pi interactions in drug-protein complexes. Here we present a fast and reliable methodology called PI (pi interactions) by NMR, which can differentiate the strength of protein-ligand CH-pi interactions in solution. By combining selective amino-acid side-chain labeling with 1 H- 13 C NMR, we are able to identify specific protein protons of side-chains engaged in CH-pi interactions with aromatic ring-systems of a ligand, based solely on 1 H chemical shift values of the interacting protein aromatic ring protons. The information encoded in the chemical shifts induced by such interactions serves as a proxy for the strength of each individual CH-pi interaction. PI by NMR changes the paradigm by which chemists can optimize the potency of drug candidates: direct determination of individual pi-interactions rather than averaged measures of all interactions. PI by NMR: Probing CH-pi Interactions in Protein-Ligand Complexes by NMR.,Platzer G, Mayer M, Beier A, Bruschweiler S, Fuchs JE, Engelhardt H, Geist L, Bader G, Schorghuber J, Lichtenecker R, Wolkersdorfer B, Kessler D, McConnell DB, Konrat R Angew Chem Int Ed Engl. 2020 May 18. doi: 10.1002/anie.202003732. PMID:32421895[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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