Crystallographic studies of the interactions of Escherichia coli lytic transglycosylase Slt35 with peptidoglycan

Lyric transglycosylases catalyze the cleavage of the beta-1,4-glycosidic bo nd between N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) i n peptidoglycan with concomitant formation of a 1,6-anhydro bond in the Mur NAc residue. To understand the reaction mechanism of Escherichia coli lytic transglycosylase Slt35, three crystal structures have been determined of S lt35 in complex with two different peptidoglycan fragments and with the lyr ic transglycosylase inhibitor bulgecin A. The complexes define four sugar-b inding subsites (-2, -1, +1, and +2) and two peptide-binding sites in a lar ge cleft close to Glu162. The Glu162 side chain is between the -1 and +1 su gar-binding sites, in agreement with a function as catalytic acid/base. The complexes suggest additional contributions to catalysis from Ser216 and As n339, residues which are conserved among the MltB/Slt35 lytic transglycosyl ases.