A COMMON FOLD FOR PEPTIDE SYNTHETASES CLEAVING ATP TO ADP - GLUTATHIONE SYNTHETASE AND D-ALANINE-D-ALANINE LIGASE OF ESCHERICHIA-COLI

Examination of x-ray crystallographic structures shows the tertiary st ructure of D-alanine:D-alanine ligase (EC 6.3.2.4), a bacterial cell w all synthesizing enzyme, is similar to that of glutathione synthetase (EC 6.3.2.3) despite low sequence homology. Both Escherichia coli enzy mes, which convert ATP to ADP during ligation to produce peptide produ cts, are made of three domains, each folded around a 4-to 6-stranded b eta-sheet core. Sandwiched between the beta-sheets of the C-terminal a nd central domains of each enzyme is a nonclassical ATP-binding site t hat contains a common set of spatially equivalent amino acids. In each enzyme, two loops are proposed to exhibit a required flexibility that allows entry of ATP and substrates, provides protection of the acylph osphate intermediate and tetrahedral adduct from hydrolysis during cat alysis, and then permits release of products.