Эдайн А

Description

Edain A is an analogue of a linear polypeptide antibiotic produced by the bacterium Bacillus (Brevibacillus) brevis. Belongs to the group of non-ribosomal peptide antibiotics of the edeine series.

Basic Attributes

• CAS No: 52452-77-4
• Molecular Weight: 754.87462
• Exact weight: 754.434
• NSC number: 663297
• DSSTox ID: DTXSID10327513
• PSA Specifications: 360
• XLogP3: -7.9

Structure

The extremely high PSA value (360) and the strongly negative XLogP3 value (-7.9) reflect the polar peptide nature of the molecule with multiple hydroxyl, amine and amide groups - a typical property of linear non-ribosomal peptides with pronounced water solubility and low membrane permeability.

Mechanism of action

Linear non-ribosomal peptides of the edeine series bind to the 30S subunit of the ribosome and block the binding of tRNA to the P-site, which disrupts protein synthesis in the bacterial cell. Exogenous edeine inhibits the synthesis of DNA and protein, but not RNA.

Producer and sustainability

Produced by Brevibacillus (Bacillus) brevis strains. The producing bacterium has developed a self-defense mechanism: the enzyme EdeQ, similar in structure to spermidine-N-acetyltransferases, converts edeine into N-acetyledeine, a form that is inactive against cells in vivo and in cell-free extracts. Acetylation of edeine by the EdeQ enzyme deprives it of its ability to suppress translation, providing resistance of the producing strain to its own antibiotic.

Edaine family

In addition to edaine A, a number of related linear peptides have been described in Brevibacillus brevis - edeine A1, B and D, differing in the composition of the unusual amino acids included in the chain, such as isoserine and beta-tyrosine, characteristic of this class of non-ribosomal peptide antibiotics. The diversity of edeine forms within one producing strain is a typical example of the combinatorial biosynthetic strategy of non-ribosomal peptide synthetases, when one biosynthetic cluster generates a spectrum of closely related molecules with slightly different antibacterial activity and toxicity profiles, which expands the arsenal of compounds available for comparative structure-function studies.

Scope of application

Research reagent for studying the mechanisms of inhibition of bacterial translation and the functioning of the 30S ribosomal subunit. Used in microbiological and biochemical laboratories.

Role in the study of the ribosome

The binding of edeines to the 30S subunit affects the region overlapping the decoding center of the ribosome and the tRNA P-binding site, therefore such peptides are used in structural biology as a tool for mapping functionally significant regions of the small subunit. Together with other translation inhibitors - streptomycin, kanamycin, tetracycline - edeines are included in the standard set of reagents for differentiating the stages of initiation, elongation and termination of protein synthesis in vitro, which makes drugs of this group in demand in molecular biology laboratories studying the mechanisms of action of ribosomal antibiotics and the development of new antimicrobial agents aimed at the bacterial translation apparatus.