Structure of the d-Cycloserine-Resistant Variant D322N of Alanine Racemase from <i>Mycobacterium tuberculosis</i>.

ABSTRACT: Alanine racemase (Alr) is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes the racemization of l-alanine to d-alanine. Alr is one of the two targets of the broad-spectrum antibiotic d-cycloserine (DCS), a structural analogue of d-alanine. Despite being an essential component of regimens used to treat multi- and extensively drug-resistant tuberculosis for almost seven decades, resistance to DCS has not been observed in patients. We previously demonstrated that DCS evades resistance due to an ultralow rate of emergence of mutations. Yet, we identified a single polymorphism (converting Asp322 to Asn) in the alr gene, which arose in 8 out of 11 independent variants identified and that confers resistance. Here, we present the crystal structure of the Alr variant D322N in both the

SUBMITTER: de Chiara C 

PROVIDER: S-EPMC10288493 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature