STRUCTURE OF A COMPLEX BETWEEN BULGECIN, A BACTERIAL METABOLITE, AND LYSOZYME FROM THE RAINBOW-TROUT

Bulgecin, a sulfonated glycopeptide produced by Pseudomonas acidophila and Pseudomonas mesoacidophila, induces bulge formation and enhances lysis of bacterial cell walls when used in combination with beta-lacta m antibiotics. The compound does not itself exhibit any antibacterial activity, but has been shown to inhibit a soluble lyric transglycosyla se (SLT70) from Escherichia coil which has a lysozyme-like domain. Rec ently, the crystal structure of an SLT-bulgecin complex has been deter mined to 3.5 Angstrom resolution. We report here the crystal structure of a complex between lysozyme from the rainbow trout (RBTL) and bulge cin A at 2.0 Angstrom resolution. As for the SLT-bulgecin complex, bul gecin is bound with the glycosaminyl moiety in subsite C and the proli ne residue in site D of the active-site cleft of RBTL, where it makes hydrogen-bonding interactions with the catalytic residues. The taurine moiety is bound to the left side of subsites E and F in the lower par t of the active-site cleft. From the observed position of the bulgecin molecule, it seems reasonable that it is an inhibitor of rainbow trou t lysozyme. The lysozymes may, in general, be a target for the design of a novel type of antibiotics distinct from the beta-lactams which ar e insensitive to the muramidases.