Maturation of the translation inhibitor microcin C

Anastasia Metlitskaya1, Teymur Kazakov, Gaston H Vondenhoff

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

Journal of Bacteriology
|January 27, 2009
PubMed

Insights

Microcin C (McC) is a bacterial growth inhibitor. Its maturation involves specific gene products (mccD and mccE) that attach a 3-aminopropyl group, enhancing its potency against aspartyl-tRNA synthetase.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Microcin C (McC) is a heptapeptide antibiotic with a unique N-acyl phosphamidate bond linking a modified AMP residue.
  • McC inhibits the growth of enteric bacteria by targeting aspartyl-tRNA synthetase.

Purpose of the Study:

  • To identify maturation intermediates of Microcin C.
  • To elucidate the roles of specific genes in the biosynthesis and maturation of Microcin C.
  • To understand how post-translational modifications affect Microcin C's inhibitory activity.

Main Methods:

  • Analysis of maturation intermediates in mutant strains lacking individual mcc biosynthesis genes.
  • Biochemical characterization of Microcin C and its precursors.

Main Results:

  • The products of the mccD and mccE genes are essential for the attachment of a 3-aminopropyl group to the phosphate of Microcin C.
  • This 3-aminopropyl modification significantly increases the potency of Microcin C's inhibition of aspartyl-tRNA synthetase.

Conclusions:

  • The maturation pathway of Microcin C involves specific enzymatic steps, including the addition of a 3-aminopropyl group.
  • This modification is crucial for the enhanced biological activity of Microcin C against its target enzyme.

Related Concept Videos

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...
Bacterial Protein Maturation01:26

Bacterial Protein Maturation

Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
Improving Translational Accuracy02:07

Improving Translational Accuracy

Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
Initiation of Translation02:33

Initiation of Translation

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
Initiation of Translation02:33

Initiation of Translation

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
Translation in Prokaryotes01:29

Translation in Prokaryotes

Prokaryote translation is a complex, highly coordinated process that converts genetic information from mRNA into functional proteins. It involves three stages: initiation, elongation, and termination, each facilitated by specific molecular components.Initiation of TranslationThe process begins with the assembly of the ribosomal subunits and initiation factors on the mRNA. In bacteria, the 30S ribosomal subunit recognizes the Shine-Dalgarno sequence in the mRNA, a conserved region upstream of...