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Crystal Structure of the first bromodomain of BRD4 in complex with DMSOCrystal Structure of the first bromodomain of BRD4 in complex with DMSO
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 PubMedBromodomains are involved in the regulation of chromatin architecture and transcription through the recognition of acetylated lysines in histones and other proteins. Many of them are considered to be relevant pharmacological targets for different pathologies. Three crystallographic structures of the N-terminal bromodomain of BRD4 in complex with low-molecular-weight fragments are presented. They show that similar molecules mimicking acetylated lysine bind the bromodomain with different orientations and exploit different interactions. It is also advised to avoid DMSO when searching for low-affinity fragments that interact with bromodomains since DMSO binds in the acetylated lysine-recognition pocket of BRD4. Different orientations of low-molecular-weight fragments in the binding pocket of a BRD4 bromodomain.,Lolli G, Battistutta R Acta Crystallogr D Biol Crystallogr. 2013 Oct;69(Pt 10):2161-4. doi:, 10.1107/S090744491301994X. Epub 2013 Sep 20. PMID:24100334[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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