Hot Spots for Protein Partnerships at the Surface of Cholinesterases and Related α/β Hydrolase Fold Proteins or Domains—A Structural Perspective

Abstract

The hydrolytic enzymes acetyl- and butyryl-cholinesterase, the cell adhesion molecules neuroligins, and the hormonogenic macromolecule thyroglobulin are a few of the many members of the α/β hydrolase fold superfamily of proteins. Despite their distinctive functions, their canonical subunits, with a molecular surface area of ~20,000 Å2, they share binding patches and determinants for forming homodimers and for accommodating structural subunits or protein partners. Several of these surface regions of high functional relevance have been mapped through structural or mutational studies, while others have been proposed based on biochemical data or molecular docking studies. Here, we review these binding interfaces and emphasize their specificity versus potentially multifunctional character.

Gallic Acid as a Non-Selective Inhibitor of α/β-Hydrolase Fold Enzymes Involved in the Inflammatory Process: The Two Sides of the Same Coin

“…These enzymes are designated as PLA2 associated with lipoprotein (Lp-PLA2) and play a role in the special regulation of extracellular PAF concentration produced during inflammation, which is induced by the phospholipase A2 cascade that includes Arachidonic Acid (AA) production [8][9][10]. Other important enzymes that exhibit a similar protein α/β hydrolase fold are the Cholinesterase-like enzymes [11] and both types of cytosolic (cPLA2) and secretory phospholipase A2 (sPLA2) found in cells and snake venom, respectively [12]. sPLA2 is a type of α/β hydrolase folding enzyme, and this structural motif is also found in several enzymes which are involved in the inflammatory process resolution, such as PAF-AH and acetylcholinesterase [11,12].…”

“…Other important enzymes that exhibit a similar protein α/β hydrolase fold are the Cholinesterase-like enzymes [11] and both types of cytosolic (cPLA2) and secretory phospholipase A2 (sPLA2) found in cells and snake venom, respectively [12]. sPLA2 is a type of α/β hydrolase folding enzyme, and this structural motif is also found in several enzymes which are involved in the inflammatory process resolution, such as PAF-AH and acetylcholinesterase [11,12].…”