Inhibitory mechanism of the Q lysis protein A2. Academic Article uri icon

abstract

  • The lysis protein A2 , present as a single copy on the surface of Q virion particles, was previously shown to inhibit the activity of MurA, an enzyme that catalyses the first committed step of murein biosynthesis. Here we report experiments with a two-hybrid study that indicates A2 and MurA interact directly. Moreover, experiments with a soluble MBP-A2 fusion indicate that the interaction between MurA and A2 is dependent on a substrate-induced conformational change featured in the UDP-NAG-liganded state of MurA but not the tetrahedral intermediate state. Moreover, based on the location of L138Q, the original dominant A2 -resistant mutant that identified MurA as the target, a directed mutagenesis strategy has identified a continuous surface required for A2 binding. This surface spans the catalytic loop/cleft and encompasses both the catalytic and C-terminal domains. These data support a model in which A2 preferentially binds MurA liganded with UDP-NAG, thereby preventing catalysis by occluding PEP from accessing the active site.

published proceedings

  • Mol Microbiol

author list (cited authors)

  • Reed, C. A., Langlais, C., Kuznetsov, V., & Young, R.

citation count

  • 12

complete list of authors

  • Reed, CA||Langlais, C||Kuznetsov, V||Young, R

publication date

  • November 2012

publisher