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Related Experiment Videos

Penicillin and beyond: evolution, protein fold, multimodular polypeptides, and multiprotein complexes

J M Ghuysen1, P Charlier, J Coyette

  • 1Centre d'Ingénierie des Protéines, Université de Liège, Sart Tilman, Belgium.

Microbial Drug Resistance (Larchmont, N.Y.)
|July 1, 1996
PubMed
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Protein evolution drives new enzyme functions through structural changes and complex formation. This study revisits bacterial cell wall synthesis, highlighting how existing proteins are modified to create novel functions, impacting antibiotic action.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Evolutionary Biology

Background:

  • Expanding protein databases enhance understanding of protein relationships, superfamilies, and evolutionary mechanisms.
  • The bacterial cell wall peptidoglycan synthesis pathway is a key area for studying protein evolution.
  • Existing proteins are known to evolve new functions through various mechanisms.

Purpose of the Study:

  • To re-examine the synthesis of bacterial cell wall peptidoglycan using recent advances in protein science.
  • To illustrate how new enzyme functions emerge from the modification of existing proteins.
  • To connect these evolutionary concepts to the action of glycopeptide and beta-lactam antibiotics.

Main Methods:

  • Analysis of protein sequence and structure databases.

Related Experiment Videos

  • Revisiting key reactions in peptidoglycan synthesis.
  • Examining the formation, utilization, and hydrolysis of the D-alanyl-D-alanine dipeptide.
  • Investigating the mechanisms of glycopeptide and beta-lactam antibiotic action.

    • Main Results:

    • Protein evolution, driven by tinkering with existing proteins, leads to new enzyme functions.
    • Mechanisms include acquiring local structural changes, fusing into multimodular polypeptides, and associating into multiprotein complexes.
    • The D-alanyl-D-alanine pathway and antibiotic targets exemplify these evolutionary processes.

    Conclusions:

    • New enzyme functions arise from the evolutionary modification of pre-existing protein structures and complexes.
    • Understanding these evolutionary pathways provides insights into antibiotic resistance and development.
    • The study reinforces the concept of evolutionary tinkering in shaping protein function and biological pathways.