A Protein Antibiotic in the Phage Qβ Virion: Diversity in Lysis Targets

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Abstract
A2, a capsid protein of RNA phage Qβ, is also responsible for host lysis. A2 blocked synthesis of murein precursors in vivo by inhibiting MurA, the catalyst of the committed step of murein biosynthesis. An A2-resistance mutation mapped to an exposed surface near the substrate-binding cleft of MurA. Moreover, purified Qβ virions inhibited wild-type MurA, but not the mutant MurA, in vitro. Thus, the two small phages characterized for their lysis strategy, Qβ and the small DNA phage φX174, effect host lysis by targeting different enzymes in the multistep, universally conserved pathway of cell wall biosynthesis.