"Open" structures of MurD: Domain movements and structural similarities with folylpolyglutamate synthetase

UDP-N-acetylmuramoyl-L-alanine:D-glutamate (MurD) ligase catalyses the addi tion of D-glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alan ine (UMA). The crystal structures of Escherichia coli in the substrate-free form and MurD complexed with UMA have been determined at 2.4 Angstrom and 1.88 Angstrom resolution, respectively. The MurD structure comprises three domains each of a topology reminiscent of nucleotide-binding folds. In the two structures the C-terminal domain undergoes a large rigid-body rotation away from the N-terminal and central domains. These two "open" structures w ere compared with the four published "closed" structures of MurD. In additi on the comparison reveals which regions are affected by the binding of UMA, ATP and D-Glu. Also we compare and discuss two structurally characterized enzymes which belong to the same ligase superfamily: MurD and folylpolyglut amate synthetase (FGS). The analysis allows the identification of key resid ues involved in the reaction mechanism of FGS. The determination of the two "open" conformation structures represents a new step towards the complete elucidation of the enzymatic mechanism of the MurD ligase. (C) 2000 Academi c Press.