PDBsum entry 5a5p

Hydrolase

PDB id: 5a5p

Contents

Protein chain

130 a.a.

Ligands

EDO ×2

JTF

SO4

Waters ×215

PDB id:

5a5p

Name:

Hydrolase

Title:

Crystal structure of human atad2 bromodomain in complex with 8-2- (dimethylamino)ethylamino-3-methyl-1,2-dihydroquinolin-2-one

Structure:

Atpase family aaa domain-containing protein 2. Chain: a. Fragment: bromodomain, residues 981-1108. Synonym: aaa nuclear coregulator cancer-associated protein, ancca, human atpase family aaa domain-containing protein 2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.03Å R-factor: 0.189 R-free: 0.208

Authors:

C.Chung,P.Bamborough,E.Demont

Key ref:

E.H.Demont et al. (2015). Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors. J Med Chem, 58, 5649-5673. PubMed id: 26155854 DOI: 10.1021/acs.jmedchem.5b00772

Date:

20-Jun-15 Release date: 22-Jul-15

Protein chain

Q6PL18  (ATAD2_HUMAN) -  ATPase family AAA domain-containing protein 2 from Homo sapiens

Seq: 1390 a.a.

Struc: 130 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.6.1.- - ?????

DOI no: 10.1021/acs.jmedchem.5b00772

J Med Chem 58:5649-5673 (2015)

PubMed id: 26155854

Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors.

E.H.Demont, C.W.Chung, R.C.Furze, P.Grandi, A.M.Michon, C.Wellaway, N.Barrett, A.M.Bridges, P.D.Craggs, H.Diallo, D.P.Dixon, C.Douault, A.J.Emmons, E.J.Jones, B.V.Karamshi, K.Locke, D.J.Mitchell, B.H.Mouzon, R.K.Prinjha, A.D.Roberts, R.J.Sheppard, R.J.Watson, P.Bamborough.

ABSTRACT

Overexpression of ATAD2 (ATPase family, AAA domain containing 2) has been linked to disease severity and progression in a wide range of cancers, and is implicated in the regulation of several drivers of cancer growth. Little is known of the dependence of these effects upon the ATAD2 bromodomain, which has been categorized as among the least tractable of its class. The absence of any potent, selective inhibitors limits clear understanding of the therapeutic potential of the bromodomain. Here, we describe the discovery of a hit from a fragment-based targeted array. Optimization of this produced the first known micromolar inhibitors of the ATAD2 bromodomain.