Characterization of the oligomeric interface of Lactate Dehydrogenase-B (LDH-B) through crystallographic and molecular dynamics approaches

Abstract

Cancer cells acquired specific characteristics, called Hallmarks, such as metabolism dysregulation. It is in this context that we study Lactate Dehydrogenase, a tetrameric enzyme catalyzing the interconversion of pyruvate to L-lactate. Lactate, previously considered as a waste product, has been shown to be essential for the anabolic growth and proliferation of cancer cells. Thus, LDH is a promising target for the development of novel cancer therapies. Therefore, an emerging strategy aiming to target the oligomerization state of LDH can be considered.

This work was devoted to the structural characterization of the tetrameric interface and hotspots allowing a better understanding of the LDH tetramerization process through crystallographic and molecular dynamics approaches. Furthermore, the binding mode of small molecules interacting at the tetrameric interface of LDH has been unravelled by crystallography. The structural data have highlighted two distinct binding sites for these compounds.

Date of Award	20 Feb 2023
Original language	English
Awarding Institution	University of Namur
Sponsors	FRS-FNRS-Télévie
Supervisor	Johan Wouters (Supervisor), Yoann Olivier (President), Catherine Michaux (Jury), Raphael FREDERICK (Jury) & Jerome DE RUYCK (Jury)