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Structural and Molecular Dynamics of <i>Mycobacterium tuberculosis</i> Malic Enzyme, a Potential Anti-TB Drug Target.


ABSTRACT: Tuberculosis (TB) is the most lethal bacterial infectious disease worldwide. It is notoriously difficult to treat, requiring a cocktail of antibiotics administered over many months. The dense, waxy outer membrane of the TB-causing agent, Mycobacterium tuberculosis (Mtb), acts as a formidable barrier against uptake of antibiotics. Subsequently, enzymes involved in maintaining the integrity of the Mtb cell wall are promising drug targets. Recently, we demonstrated that Mtb lacking malic enzyme (MEZ) has altered cell wall lipid composition and attenuated uptake by macrophages. These results suggest that MEZ contributes to lipid biosynthesis by providing reductants in the form of NAD(P)H. Here, we present the X-ray crystal structure of MEZ to 3.6 Å. We use biochemical assays to demonstr

SUBMITTER: Burley KH 

PROVIDER: S-EPMC8083904 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature