Binding hotspots of BAZ2B bromodomain: Histone interaction revealed by solution NMR driven docking.

摘要: Bromodomains are epigenetic reader domains, which have come under increasing scrutiny both from academic and pharmaceutical research groups. Effective targeting of the BAZ2B bromodomain by small molecule inhibitors has been recently reported, but no structural information is yet available on interaction with its natural binding partner, acetylated histone H3K14ac. We assigned studied H3K14ac peptides NMR spectroscopy using chemical shift perturbation (CSP) data clean exchange (CLEANEX-PM) experiments. The latter was used to characterize water molecules known play an important role in mediating interactions. Besides anticipated Kac site, we consistently found BC loop as hotspots for interaction. This create a data-driven model complex HADDOCK. Our findings provide structure dynamics characterization that will be useful quest potent selective probe function bromodomain.