8WYP

High Resolution Crystal Structure of Brd4 BD-1 in Complex with a Novel Inhibitor Precursor

Summary for 8WYP

• Entry DOI: 10.2210/pdb8wyp/pdb
• Descriptor: Bromodomain-containing protein 4, 3-bromanylimidazo[1,2-a]pyridin-6-amine (3 entities in total)
• Functional Keywords: brd4 inhibitor, transcription
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 15307.28

Authors

Liu, B.,Ma, X. (deposition date: 2023-10-31, release date: 2024-05-22)

Primary citation

Ma, X.,Wang, M.,Wang, F.,Li, J.,Zhang, Z.,Zhu, J.,Liu, B.
High resolution crystal structure of BRD4-BD1 in complex with a novel inhibitor precursor.
Biochem.Biophys.Res.Commun., 690:149284-149284, 2024

PubMed Abstract: The inhibition of BRD4 bromodomain is an effective therapeutic strategy for a variety of diseases in which BRD4 are implicated. Herein, we identified a small-molecule BRD4 inhibitor hit named compound 3 using high-throughput screening. The 1.6 Å resolution co-crystal structure confirmed that the compound occupies the KAc recognition pockets of BRD4 by forming key hydrogen bonds with Asn140 and engaging in hydrophobic interactions, thus impedes the binding of acetylated lysine to BRD4. These findings suggest compound 3 can be a lead compound to develop a structurally novel BRD4 inhibitors.

PubMed: 38006801
DOI: 10.1016/j.bbrc.2023.149284

Experimental method

X-RAY DIFFRACTION (1.24 Å)