Figure 5. Scheme of CPS1 activation.

Schematic representation of the structural changes and interactions (indicated as double dashed arrows) between the different elements involved in the activation of CPS1 upon binding of NAG and the nucleotide. Ligands are shown in sticks representation. Binding of NAG alters the A-loop, which in the apo form interacts with the T′-loop from the L3 domain. This loop experiences a radical reorganization between the apo and ligand-bound forms. The T′-loop interacts also with the T-loop (from the L1-domain) influencing both ATP binding sites mainly through their interaction with the K′- and K-loops, respectively. These changes together with the remodeling of the tunnel-loop and reorientations between domains result in the building of a functional carbamate tunnel. Stabilization of the modified architecture is achieved through the C-tail fixing the relative orientations of domains L1, L3 and L4.