Structure and regulation of human phospholipase D

Adv Biol Regul. 2021 Jan:79:100783. doi: 10.1016/j.jbior.2020.100783. Epub 2021 Jan 3.

Abstract

Mammalian phospholipase D (PLD) generates phosphatidic acid, a dynamic lipid secondary messenger involved with a broad spectrum of cellular functions including but not limited to metabolism, migration, and exocytosis. As a promising pharmaceutical target, the biochemical properties of PLD have been well characterized. This has led to the recent crystal structures of human PLD1 and PLD2, the development of PLD specific pharmacological inhibitors, and the identification of cellular regulators of PLD. In this review, we discuss the PLD1 and PLD2 structures, PLD inhibition by small molecules, and the regulation of PLD activity by effector proteins and lipids.

Keywords: Cancer; Cell signaling; Phosphatidic acid; Phospholipase D; Protein structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Humans
  • Phosphatidic Acids / metabolism
  • Phospholipase D / antagonists & inhibitors
  • Phospholipase D / chemistry*
  • Phospholipase D / genetics
  • Phospholipase D / metabolism*
  • Signal Transduction

Substances

  • Enzyme Inhibitors
  • Phosphatidic Acids
  • phospholipase D2
  • Phospholipase D
  • phospholipase D1