Allosteric regulation of menaquinone (vitamin K₂) biosynthesis in the human pathogen Mycobacterium tuberculosis.

ABSTRACT: Menaquinone (vitamin K₂) plays a vital role in energy generation and environmental adaptation in many bacteria, including the human pathogen Mycobacterium tuberculosis (Mtb). Although menaquinone levels are known to be tightly linked to the cellular redox/energy status of the cell, the regulatory mechanisms underpinning this phenomenon are unclear. The first committed step in menaquinone biosynthesis is catalyzed by MenD, a thiamine diphosphate-dependent enzyme comprising three domains. Domains I and III form the MenD active site, but no function has yet been ascribed to domain II. Here, we show that the last cytosolic metabolite in the menaquinone biosynthesis pathway, 1,4-dihydroxy-2-naphthoic acid (DHNA), binds to domain II of Mtb-MenD and inhibits its ac

SUBMITTER: Bashiri G 

PROVIDER: S-EPMC7086027 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature