Related Experiment Video
Updated: Jun 4, 2026
05:32
In Vitro Chemical Mapping of G-Quadruplex DNA Structures by Bis-3-Chloropiperidines
Published on: May 12, 2023
Unusual backfolded binding poses of BAZ2A bromodomain binders
Andrea Dalle Vedove1, Giulia Cazzanelli1, Vito Giuseppe D'Agostino1
1Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, Via Sommarive 9, 38123 Povo - Trento, Italy.
Summary
Researchers explored novel compounds targeting the BAZ2A protein, crucial in prostate cancer metastasis. They identified unique BAZ2A-binding molecules, paving the way for developing potent inhibitors against this challenging cancer target.
Area of Science:
- Biochemistry
- Oncology
- Drug Discovery
Background:
- The BAZ2A protein is overexpressed in aggressive prostate cancer, promoting tumor cell migration and invasion.
- Targeting the BAZ2A bromodomain with small molecules is a strategy to inhibit its metastasis-promoting role.
- BAZ2A's shallow binding pocket presents a significant challenge for developing potent inhibitors.
Purpose of the Study:
- To explore novel chemical scaffolds for inhibiting BAZ2A.
- To identify compounds that bind to the BAZ2A bromodomain despite its challenging pocket.
- To lay the groundwork for developing potent BAZ2A macrocyclic inhibitors.
Main Methods:
- Exploration of the acetyl-pyrrole scaffold.
- Identification of BAZ2A-binding compounds.
- X-ray crystallography to determine compound conformation.
Main Results:
- Novel BAZ2A-binding compounds were identified using the acetyl-pyrrole scaffold.
- These compounds adopt a unique, enclosed conformation within the BAZ2A binding site.
- The findings provide a basis for designing potent BAZ2A inhibitors.
Conclusions:
- The acetyl-pyrrole scaffold is a promising starting point for BAZ2A inhibitor development.
- The identified compounds' unique conformation offers new insights into targeting shallow bromodomain pockets.
- This research advances the development of therapeutics for metastatic prostate cancer.
Related Concept Videos
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
02:13Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
02:13Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
02:21Globular and Fibrous Proteins
Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
02:18The Equilibrium Binding Constant and Binding Strength
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium: