Conformational switches modulate protein interactions in peptide antibiotic synthetases

Science. 2006 Apr 14;312(5771):273-6. doi: 10.1126/science.1122928.

Abstract

Protein dynamics plays an important role in protein function. Many functionally important motions occur on the microsecond and low millisecond time scale and can be characterized by nuclear magnetic resonance relaxation experiments. We describe the different states of a peptidyl carrier protein (PCP) that play a crucial role in its function as a peptide shuttle in the nonribosomal peptide synthetases of the tyrocidine A system. Both apo-PCP (without the bound 4'-phosphopantetheine cofactor) and holo-PCP exist in two different stable conformations. We show that one of the apo conformations and one of the holo conformations are identical, whereas the two remaining conformations are only detectable by nuclear magnetic resonance spectroscopy in either the apo or holo form. We further demonstrate that this conformational diversity is an essential prerequisite for the directed movement of the 4'-PP cofactor and its interaction with externally acting proteins such as thioesterases and 4'-PP transferase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoproteins / chemistry
  • Apoproteins / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Crystallography, X-Ray
  • Fatty Acid Synthases / metabolism
  • Holoenzymes / chemistry
  • Holoenzymes / metabolism
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Pantetheine / analogs & derivatives
  • Pantetheine / metabolism
  • Peptide Synthases / chemistry*
  • Peptide Synthases / metabolism*
  • Protein Conformation*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Thiolester Hydrolases / metabolism
  • Transferases / metabolism

Substances

  • Apoproteins
  • Bacterial Proteins
  • Carrier Proteins
  • Holoenzymes
  • Pantetheine
  • Transferases
  • Fatty Acid Synthases
  • Thiolester Hydrolases
  • thioesterase II
  • Peptide Synthases
  • tyrocidine synthetase
  • 4'-phosphopantetheine

Associated data

  • PDB/2GDW
  • PDB/2GDX
  • PDB/2GDY
  • PDB/2GE0