Visualizing complexes of phospholipids with Streptomyces phospholipase D by automated docking

Area of Science:

• Biochemistry
• Molecular Biology
• Enzymology

Background:

• Phospholipase D (PLD) enzymes hydrolyze phospholipids, playing roles in cell signaling and membrane remodeling.
• Streptomyces sp. PMF PLD exhibits broad substrate specificity, but the structural basis remains unclear.

Purpose of the Study:

• To investigate the binding interactions of various phospholipid substrates with the active site of Streptomyces sp. PMF phospholipase D (PLD).
• To elucidate the structural determinants of substrate selectivity in Streptomyces PLD through computational docking.

Main Methods:

• Utilized the AutoDock program for automated molecular docking.
• Docked a diverse range of phospholipids, including phosphatidic acids (PAs), phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, phosphatidylinositol, and phosphatidylserines, onto the Streptomyces PLD active site.

Main Results:

• Binding energies generally became more negative with increasing fatty acid residue length.
• Longer fatty acid chains adopted distinct binding modes, with one interacting within a hydrophobic pocket and the other on an external hydrophobic surface.
• Phosphatidylcholines exhibited unique, firm binding of their head group within the active site.

Conclusions:

• Fatty acid chain length significantly influences the binding affinity of phospholipids to Streptomyces PLD.
• The distinct head group binding of phosphatidylcholines may explain the enzyme's limited selectivity for other phospholipid substrates.
• Computational docking provides insights into the structural basis of Streptomyces PLD substrate recognition.