Abhydrolase

Abhydrolase, short for alpha/beta hydrolase domain-containing proteins, refers to a large and evolutionarily conserved superfamily of hydrolase enzymes that share a common structural fold. Members typically harbor an alpha/beta hydrolase fold and a catalytic nucleophile in a conserved motif, often part of a catalytic triad such as Ser-Asp-His, though variations with cysteine or other residues occur. The fold is characterized by a central beta-sheet flanked by alternating alpha-helices, with the active site usually situated in a loop region known as the nucleophile elbow.

Function and diversity: The ABHD family encompasses enzymes with a wide range of substrate specificities, including lipases, esterases, thioesterases, and epoxide hydrolases. They participate in lipid metabolism and signaling by hydrolyzing glycerolipids, glycerophospholipids, and related lipid-derived molecules. In many organisms, including humans, ABHD proteins display diverse subcellular localizations, being membrane-associated, cytosolic, or peroxisomal, and often contain additional domains that influence localization and regulation.

Physiological and medical relevance: The ABHD superfamily includes enzymes with important physiological roles and disease associations. Some members are under investigation as drug targets for metabolic, inflammatory, and neurological conditions. For example, certain ABHD enzymes influence endocannabinoid signaling, lipid turnover, and signaling lipid pools. Mutations or dysregulation of specific ABHD proteins have been linked to human diseases, underscoring the functional significance of this broad enzyme family.

Classification and nomenclature: ABHD stands for alpha/beta hydrolase domain-containing proteins. The term abhydrolase is sometimes used to describe the structural/functional fold rather than a single enzyme. Individual ABHD proteins are typically annotated and studied according to their specific substrate scope, localization, and biological role.