PDBsum entry 5e9l

Transcription

PDB id: 5e9l

Contents

Protein chain

116 a.a.

Ligands

6AI

Waters ×122

PDB id:

5e9l

Name:

Transcription

Title:

Crystal structure of baz2b bromodomain in complex with fragment f103

Structure:

Bromodomain adjacent to zinc finger domain protein 2b. Chain: a. Fragment: bromodomain (residues 2054-2168). Synonym: hwalp4. Engineered: yes. Other_details: first two residues sm derive from the expression tag

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: baz2b, kiaa1476. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.90Å R-factor: 0.181 R-free: 0.212

Authors:

G.Lolli,A.Caflisch

Key ref:

G.Lolli and A.Caflisch (2016). High-Throughput Fragment Docking into the BAZ2B Bromodomain: Efficient in Silico Screening for X-Ray Crystallography. Acs Chem Biol, 11, 800-807. PubMed id: 26942307 DOI: 10.1021/acschembio.5b00914

Date:

15-Oct-15 Release date: 16-Mar-16

Protein chain

Q9UIF8  (BAZ2B_HUMAN) -  Bromodomain adjacent to zinc finger domain protein 2B from Homo sapiens

Seq: 2168 a.a.

Struc: 116 a.a.*

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

DOI no: 10.1021/acschembio.5b00914

Acs Chem Biol 11:800-807 (2016)

PubMed id: 26942307

High-Throughput Fragment Docking into the BAZ2B Bromodomain: Efficient in Silico Screening for X-Ray Crystallography.

G.Lolli, A.Caflisch.

ABSTRACT

Bromodomains are protein modules that bind to acetylated lysine side chains in histones and other proteins. The bromodomain adjacent to zinc finger domain protein 2B (BAZ2B) has been reported to be poorly druggable. Here, we screened an in-house library of 350 fragments by automatic docking to the BAZ2B bromodomain. The top 12 fragments according to the predicted binding energy were selected for experiments of soaking into apo crystals of BAZ2B which yielded the structure of the complex for four of them, which is a hit rate of 33%. Additional crystal structures were solved for BAZ2B and two scaffolds identified by analogy. For three topologically similar fragments, the crystal structures reveal binding modes with different penetration, i.e., with zero, one, and two water molecules, respectively, located between the fragment and the side chain of a conserved tyrosine (Tyr1901) in the bottom of the acetyl lysine pocket of BAZ2B. Furthermore, a remarkable stereoselectivity of the acetyl lysine pocket emerges from the crystal structures of the bromodomains of BAZ2B and SMARCA4 in complex with the chiral diol MPD (2-methyl-2,4-pentanediol).