Figure 6

Regulation of DAHPS enzyme activity by the CM2 domain. Panel (A) shows the basic architecture of DAHPS-CM domain dimers in the absence of a CM2-ligand. Panel (B) shows the substrate (rectangular black box) binding at the active site of the DAHPS domain in the absence of a CM2-ligand. In panel (C), CM2-ligand (oval black box) binds at the active site of CM2, which leads to the conformational changes in linker region and loop L1, which connects helices H1-H2. The linker region adopts the kinked conformation and brings the DAHPS and CM2 domains near to each other. Loop L1 extends outward and flips side chains of loop residues. Loop L1 mediates the domain-domain interface formation between DAHPS and CM2 domains and blocks the DAHPS-substrate access to the DAHPS-active site. As shown in panel (D), the DAHPS domain undergoes conformational changes, which will hinder in the binding of substrate at the active site of this domain. For simplicity, the only dimer of DAHPS has been shown instead of the tetramer.