An Unusual "OR" Gate for Allosteric Regulation of Mammalian Transglutaminase 2 in the Extracellular Matrix.

ABSTRACT: Transglutaminase 2 (TG2) is a highly expressed mammalian enzyme whose biological function is unclear, although its catalytic activity in the small intestine appears necessary for celiac disease (CeD) pathogenesis. While TG2 activity is reversibly regulated by multiple allosteric mechanisms, their roles under fluctuating physiological conditions are not well understood. Here, we demonstrate that extracellular TG2 activity is competitively controlled by the mutually exclusive binding of a high-affinity Ca²⁺ ion or the formation of a strained disulfide bond. Binding of Ca²⁺ at the high-affinity site does not activate TG2 per se, but it protects against oxidative enzyme deactivation while preserving the ability of Ca²⁺ ions to occupy weaker binding sites

SUBMITTER: Melkonian AV 

PROVIDER: S-EPMC9635980 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature