PDBsum entry 4qzs

Transcription

PDB id: 4qzs

Contents

Protein chain

127 a.a.

Ligands

JQ1

EDO ×2

Metals

_CL

Waters ×172

PDB id:

4qzs

Name:

Transcription

Title:

Crystal structure of the first bromodomain of human 3-fluoro tyrosine- labeled brd4 in complex with jq1

Structure:

Bromodomain-containing protein 4. Chain: a. Fragment: bromo 1 domain residues 44-168. Synonym: protein hunk1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: brd4, hunk1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.45Å R-factor: 0.140 R-free: 0.185

Authors:

S.W.Ember,E.Schonbrunn

Key ref:

N.K.Mishra et al. (2014). Fluorinated aromatic amino acids are sensitive 19F NMR probes for bromodomain-ligand interactions. Acs Chem Biol, 9, 2755-2760. PubMed id: 25290579 DOI: 10.1021/cb5007344

Date:

28-Jul-14 Release date: 29-Oct-14

Protein chain

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

Seq: 1362 a.a.

Struc: 127 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

DOI no: 10.1021/cb5007344

Acs Chem Biol 9:2755-2760 (2014)

PubMed id: 25290579

Fluorinated aromatic amino acids are sensitive 19F NMR probes for bromodomain-ligand interactions.

N.K.Mishra, A.K.Urick, S.W.Ember, E.Schönbrunn, W.C.Pomerantz.

ABSTRACT

We describe a (19)F NMR method for detecting bromodomain-ligand interactions using fluorine-labeled aromatic amino acids due to the conservation of aromatic residues in the bromodomain binding site. We test the sensitivity, accuracy, and speed of this method with small molecule ligands (+)-JQ1, BI2536, Dinaciclib, TG101348, and acetaminophen using three bromodomains Brd4, BrdT, and BPTF. Simplified (19)F NMR spectra allowed for simultaneous testing of multiple bromodomains to assess selectivity and identification of a new BPTF ligand. Fluorine labeling only modestly affected the Brd4 structure and function assessed by isothermal titration calorimetry, circular dichroism, and X-ray crystallography. The speed, ease of interpretation, and low concentration of protein needed for binding experiments affords a new method to discover and characterize both native and new ligands.