Discovery of a novel lactate dehydrogenase tetramerization domain using epitope mapping and peptides.

ABSTRACT: Despite being initially regarded as a metabolic waste product, lactate is now considered to serve as a primary fuel for the tricarboxylic acid cycle in cancer cells. At the core of lactate metabolism, lactate dehydrogenases (LDHs) catalyze the interconversion of lactate to pyruvate and as such represent promising targets in cancer therapy. However, direct inhibition of the LDH active site is challenging from physicochemical and selectivity standpoints. However, LDHs are obligate tetramers. Thus, targeting the LDH tetrameric interface has emerged as an appealing strategy. In this work, we examine a dimeric construct of truncated human LDH to search for new druggable sites. We report the identification and characterization of a new cluster of interactions in the LDH tetrameric interface. Usi

SUBMITTER: Thabault L 

PROVIDER: S-EPMC8010463 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature