Structure of a complex between bulgecin, a bacterial metabolite, and lysozyme from the rainbow trout.

Abstract

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-lactam antibiotics. The compound does not itself exhibit any antibacterial activity, but has been shown to inhibit a soluble lytic transglycosylase (SLT70) from Escherichia coli which has a lysozyme-like domain. Recently, the crystal structure of an SLT-bulgecin complex has been determined to 3.5 A resolution. We report here the crystal structure of a complex between lysozyme from the rainbow trout (RBTL) and bulgecin A at 2.0 A resolution. As for the SLT-bulgecin complex, bulgecin is bound with the glycosaminyl moiety in subsite C and the proline 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 part of the active-site cleft. From the observed position of the bulgecin molecule, it seems reasonable that it is an inhibitor of rainbow trout lysozyme. The lysozymes may, in general, be a target for the design of a novel type of antibiotics distinct from the beta-lactams which are insensitive to the muramidases.