PDBsum entry 5lj1

Transcription

PDB id: 5lj1

Contents

Protein chain

127 a.a.

Ligands

EDO

6XX

Waters ×164

PDB id:

5lj1

Name:

Transcription

Title:

N-terminal bromodomain of human brd4 with 8-(((3r,4r,5s)-3-((4,4- difluorocyclohexyl)methoxy)-5-methoxypiperidin-4-yl)amino)-3-methyl- 5-(5-methylpyridin-3-yl)-1,7-naphthyridin-2(1h)-one

Structure:

Bromodomain-containing protein 4. Chain: a. Synonym: protein hunk1. Engineered: yes. Other_details: sm residues residual after cleavage of expression tag

Source:

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

Resolution:

1.90Å R-factor: 0.171 R-free: 0.237

Authors:

C.Chung,P.Bamborough,E.Demont

Key ref:

P.Bamborough et al. (2016). A Chemical Probe for the ATAD2 Bromodomain. Angew Chem Int Ed Engl, 55, 11382-11386. PubMed id: 27530368 DOI: 10.1002/anie.201603928

Date:

17-Jul-16 Release date: 31-Aug-16

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 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1002/anie.201603928

Angew Chem Int Ed Engl 55:11382-11386 (2016)

PubMed id: 27530368

A Chemical Probe for the ATAD2 Bromodomain.

P.Bamborough, C.W.Chung, E.H.Demont, R.C.Furze, A.J.Bannister, K.H.Che, H.Diallo, C.Douault, P.Grandi, T.Kouzarides, A.M.Michon, D.J.Mitchell, R.K.Prinjha, C.Rau, S.Robson, R.J.Sheppard, R.Upton, R.J.Watson.

ABSTRACT

ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF2 as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2) using 1,3-interactions to control the conformation of a piperidine ring. This resulted in the first reported low-nanomolar, selective and cell permeable chemical probe for ATAD2.