Related Experiment Video

Updated: Aug 9, 2026

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
11:56

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids

Published on: May 4, 2018

Aspartyl-tRNA synthetase is the target of peptide nucleotide antibiotic Microcin C

Anastasia Metlitskaya1, Teymur Kazakov, Aigar Kommer

  • 1Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, Russia.

The Journal of Biological Chemistry
|April 1, 2006
PubMed

Insights

Microcin C, an antibacterial peptide, inhibits bacterial growth by targeting translation. Its degradation product specifically blocks aspartyl-tRNA synthetase, halting protein synthesis.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Microcin C is a ribosome-synthesized heptapeptide with a unique modified adenosine monophosphate.
  • It is known to be a potent inhibitor of bacterial cell growth, targeting translation.
  • The precise mechanism of Microcin C's inhibition of bacterial translation remained undefined.

Purpose of the Study:

  • To elucidate the undefined mechanism by which Microcin C inhibits bacterial translation.
  • To identify the specific molecular target and degradation products of Microcin C within sensitive cells.

Main Methods:

  • In vivo kinetic analysis of macromolecular synthesis inhibition.
  • Characterization of Microcin C degradation products within bacterial cells.
  • Biochemical assays to assess the inhibitory activity of degradation products on translation machinery.

Main Results:

  • Microcin C undergoes specific degradation within sensitive bacterial cells.
  • The primary degradation product is a modified aspartyl-adenylate with an N-acylphosphoramidate linkage.
  • This aspartyl-adenylate derivative potently inhibits bacterial translation by blocking aspartyl-tRNA synthetase activity.

Conclusions:

  • Microcin C's antibacterial activity is mediated by its degradation product.
  • The degradation product acts as a specific inhibitor of aspartyl-tRNA synthetase, a crucial enzyme in protein synthesis.
  • This study defines the mechanism of action for Microcin C, revealing a novel strategy for bacterial translation inhibition.

More Related Videos

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins11:25

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins

Published on: October 4, 2017

Isolation of Translating Ribosomes Containing Peptidyl-tRNAs for Functional and Structural Analyses11:19

Isolation of Translating Ribosomes Containing Peptidyl-tRNAs for Functional and Structural Analyses

Published on: February 25, 2011

Related Concept Videos

tRNA Activation02:26

tRNA Activation

Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Amino Acid Catabolism01:18

Amino Acid Catabolism

Microorganisms rely on proteins as an essential carbon and energy source, particularly in environments with limited polysaccharides or lipids. However, proteins are too large to cross the plasma membrane unaided, necessitating enzymatic degradation. Microbes secrete extracellular proteases and peptidases that hydrolyze proteins into peptides, which can then be transported across the membrane. Once inside the cell, intracellular proteases degrade these peptides into free amino acids, which...
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
Transcription Attenuation in Prokaryotes02:42

Transcription Attenuation in Prokaryotes

Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...