PDBsum entry 6fgw

Transcription

PDB id: 6fgw

Contents

Protein chain

103 a.a.

Ligands

D9Q

Waters ×13

PDB id:

6fgw

Name:

Transcription

Title:

Crystal structure of baz2a bromodomain in complex with 1- methylpyridinone compound 4

Structure:

Bromodomain adjacent to zinc finger domain protein 2a. Chain: a. Synonym: transcription termination factor i-interacting protein 5, tip5,hwalp3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: baz2a, kiaa0314, tip5. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.73Å R-factor: 0.223 R-free: 0.254

Authors:

A.Dalle Vedove,D.Spiliotopoulos,G.Lolli,A.Caflisch

Key ref:

A.Dalle Vedove et al. (2018). Structural Analysis of Small-Molecule Binding to the BAZ2A and BAZ2B Bromodomains. ChemMedChem, 13, 1479-1487. PubMed id: 29770599 DOI: 10.1002/cmdc.201800234

Date:

11-Jan-18 Release date: 30-May-18

Protein chain

Q9UIF9  (BAZ2A_HUMAN) -  Bromodomain adjacent to zinc finger domain protein 2A from Homo sapiens

Seq: 1905 a.a.

Struc: 103 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1002/cmdc.201800234

ChemMedChem 13:1479-1487 (2018)

PubMed id: 29770599

Structural Analysis of Small-Molecule Binding to the BAZ2A and BAZ2B Bromodomains.

A.Dalle Vedove, D.Spiliotopoulos, V.G.D'Agostino, J.R.Marchand, A.Unzue, C.Nevado, G.Lolli, A.Caflisch.

ABSTRACT

The bromodomain-containing protein BAZ2A is a validated target in prostate cancer research, whereas the function of its paralogue BAZ2B is still undefined. The bromodomains of BAZ2A and BAZ2B have a similar binding site for their natural ligand, the acetylated lysine side chain. Here, we present an analysis of the binding modes of eight compounds belonging to three distinct chemical classes. For all compounds, the moiety mimicking the natural ligand engages in essentially identical interactions in the BAZ2A and BAZ2B bromodomains. In contrast, the rest of the molecule is partially solvent-exposed and adopts different orientations with different interactions in the two bromodomains. Some of these differences could be exploited for designing inhibitors with selectivity within the BAZ2 bromodomain subfamily.