Evolutionarily divergent <i>Mycobacterium tuberculosis</i> CTP synthase filaments are under selective pressure.

ABSTRACT: The final and rate-limiting enzyme in pyrimidine biosynthesis, CTP synthase (CTPS) , is essential for the viability of Mycobacterium tuberculosis and other mycobacteria. Its product, CTP, is critical for RNA, DNA, lipid and cell wall synthesis, and is involved in chromosome segregation. In various organisms across the tree of life, CTPS assembles into higher-order filaments, leading us to hypothesize that M. tuberculosis CTPS (mtCTPS) also forms higher-order structures. Here, we show that mtCTPS does assemble into filaments but with an unusual architecture not seen in other organisms. Through a combination of structural, biochemical, and cellular techniques, we show that polymerization stabilizes the active conformation of the enzyme and resists product inhibition, potentiall

SUBMITTER: Lynch EM 

PROVIDER: S-EPMC11291164 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature