PDBsum entry 5ig6

Transcription

PDB id: 5ig6

Contents

Protein chain

115 a.a.

Ligands

GOL ×2

6B3

Metals

_CL ×2

Waters ×240

PDB id:

5ig6

Name:

Transcription

Title:

Ultra-high resolution crystal structure of second bromodomain of brd2 in complex with inhibitor 6b3

Structure:

Bromodomain-containing protein 2. Chain: a. Fragment: unp residues 348-454. Synonym: o27.1.1,really interesting new gene 3 protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: brd2, kiaa9001, ring3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008

Resolution:

0.91Å R-factor: 0.126 R-free: 0.143

Authors:

S.K.Tripathi,B.Padmanabhan

Key ref:

S.Tripathi et al. (2016). A Novel Phenanthridionone Based Scaffold As a Potential Inhibitor of the BRD2 Bromodomain: Crystal Structure of the Complex. Plos One, 11, e0156344. PubMed id: 27243809 DOI: 10.1371/journal.pone.0156344

Date:

27-Feb-16 Release date: 22-Jun-16

Protein chain

P25440  (BRD2_HUMAN) -  Bromodomain-containing protein 2 from Homo sapiens

Seq: 801 a.a.

Struc: 115 a.a.*

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

DOI no: 10.1371/journal.pone.0156344

Plos One 11:e0156344 (2016)

PubMed id: 27243809

A Novel Phenanthridionone Based Scaffold As a Potential Inhibitor of the BRD2 Bromodomain: Crystal Structure of the Complex.

S.Tripathi, S.Mathur, P.Deshmukh, R.Manjula, B.Padmanabhan.

ABSTRACT

Bromodomain containing proteins recognize the level of histone acetylation and regulate epigenetically controlled processes like gene transcription and chromatin modification. The BET (bromodomain and extra-terminal) family proteins, which are transcriptional co-regulators, have been implicated in the pathogenesis of cancer, neurodegenerative disorders, and defects in embryonic stem cell differentiation. Inhibitors selectively targeting the BET bromodomains can pave the path for new drug discovery against several forms of major diseases. By a rational structure-based approach, we have identified a new inhibitor (NSC127133) of the second bromodomain (BD2) of the BET family protein BRD2 using the NCI Diversity Set III library. A high-resolution crystal structure of the BRD2-BD2 in complex with this compound and in apo- form is refined to 0.91 and 0.94 Å, respectively. The compound, which is a phenanthridinone derivative, binds well to the acetyl-lysine binding pocket of BD2 and displays significant hydrophobic and hydrophilic interactions. Moreover, the atomic resolution data obtained in this study allowed us to visualize certain structural features of BD2 which remained unobserved so far. We propose that the discovered compound may be a potential molecule to develop a new library for inhibiting the BRD2-BD2 function.