Solution structure of B. subtilis acyl carrier protein

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biology

Background:

• Acyl carrier protein (ACP) is crucial for fatty acid biosynthesis, carrying the growing chain via its 4'-phosphopantetheine (4'-PP) group.
• Holo-acyl carrier protein synthase (ACPS) activates ACP by transferring 4'-PP from coenzyme A (CoA) to a specific serine residue.
• Both ACP and ACPS are essential for E. coli viability and represent potential antibiotic targets.

Purpose of the Study:

• To determine the solution structure of Bacillus subtilis ACP.
• To elucidate the structural basis of ACP activation by ACPS.

Main Methods:

• Two-dimensional and three-dimensional heteronuclear NMR spectroscopy.
• Hybrid distance geometry-simulated annealing calculations.
• Analysis of 1,050 experimental NMR restraints.

Main Results:

• The solution structure of B. subtilis ACP (9 kDa) was determined, revealing a compact four alpha-helical bundle.
• The 4'-PP prosthetic group is attached to Ser36, located in alpha helix II.
• Structural comparison with E. coli ACP and act apo-ACP showed conserved secondary structures but significant differences in overall fold, likely due to methodological limitations.

Conclusions:

• The apo and holo forms of ACP exhibit nearly identical structures.
• ACPS binding induces a conformational change in ACP, displacing helix II near Ser36.
• This perturbation facilitates the transfer of 4'-PP from CoA to ACP, highlighting a key step in fatty acid synthesis.