PDBsum entry 5nne

Transcription

PDB id: 5nne

Contents

Protein chain

125 a.a.

Ligands

GLY-LYS-ALA-ALY-GLY-LYS-ALY-THR-GLN-MET

EDO

Waters ×142

PDB id:

5nne

Name:

Transcription

Title:

Crystal structure of the first bromodomain of human brd4 in complex with a diacetylated top2a peptide (k1201ac/k1204ac)

Structure:

Bromodomain-containing protein 4. Chain: a. Synonym: protein hunk1. Engineered: yes. Gka(aly)gk(aly)tqmy. Chain: c. Engineered: yes. Other_details: top2a peptide acetylated at k1201 and k1204. Additional c-terminal tyr added for uv detection

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: brd4, hunk1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: r3. Synthetic: yes. Organism_taxid: 9606

Resolution:

1.15Å R-factor: 0.140 R-free: 0.164

Authors:

P.Filippakopoulos,S.Picaud,T.Krojer,F.Von Delft,C.H.Arrowsmith, A.M.Edwards,C.Bountra

Key ref:

J.P.Lambert et al. (2019). Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains. Mol Cell, 73, 621. PubMed id: 30554943 DOI: 10.1016/j.molcel.2018.11.006

Date:

08-Apr-17 Release date: 16-May-18

Protein chain

O60885  (BRD4_HUMAN) -  Bromodomain-containing protein 4 from Homo sapiens

Seq: 1362 a.a.

Struc: 125 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/j.molcel.2018.11.006

Mol Cell 73:621 (2019)

PubMed id: 30554943

Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains.

J.P.Lambert, S.Picaud, T.Fujisawa, H.Hou, P.Savitsky, L.Uusküla-Reimand, G.D.Gupta, H.Abdouni, Z.Y.Lin, M.Tucholska, J.D.R.Knight, B.Gonzalez-Badillo, N.St-Denis, J.A.Newman, M.Stucki, L.Pelletier, N.Bandeira, M.D.Wilson, P.Filippakopoulos, A.C.Gingras.

ABSTRACT

Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, BRD3, BRD4, and BRDT following treatment with the pan-BET BRD inhibitor JQ1, revealing broad rewiring of the interaction landscape, with three distinct classes of behavior for the 603 unique interactors identified. A group of proteins associate in a JQ1-sensitive manner with BET BRDs through canonical and new binding modes, while two classes of extra-terminal (ET)-domain binding motifs mediate acetylation-independent interactions. Last, we identify an unexpected increase in several interactions following JQ1 treatment that define negative functions for BRD3 in the regulation of rRNA synthesis and potentially RNAPII-dependent gene expression that result in decreased cell proliferation. Together, our data highlight the contributions of BET protein modules to their interactomes allowing for a better understanding of pharmacological rewiring in response to JQ1.