D-Alanine-d-alanine ligase as a model for the activation of ATP-grasp enzymes by monovalent cations.

ABSTRACT: The ATP-grasp superfamily of enzymes shares an atypical nucleotide-binding site known as the ATP-grasp fold. These enzymes are involved in many biological pathways in all domains of life. One ATP-grasp enzyme, d-alanine-d-alanine ligase (Ddl), catalyzes ATP-dependent formation of the d-alanyl-d-alanine dipeptide essential for bacterial cell wall biosynthesis and is therefore an important antibiotic drug target. Ddl is activated by the monovalent cation (MVC) K⁺, but despite its clinical relevance and decades of research, how this activation occurs has not been elucidated. We demonstrate here that activating MVCs bind adjacent to the active site of Ddl from Thermus thermophilus and used a combined biochemical and structural approach to characterize MVC activation. We found

SUBMITTER: Pederick JL 

PROVIDER: S-EPMC7278361 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature