A(2), a capsid protein of RNA phage Q beta, is also responsible for host Lysis. A(2) blocked synthesis of murein precursors in vivo by inhibiting MurA, the catalyst of the committed step of murein biosynthesis. An A(2)-resistance mutation mapped to an exposed surface near the substrate-binding cleft of MurA. Moreover, purified Q beta virions inhibited wild-type MurA, but not the mutant MurA, in vitro. Thus, the two small phages characterized for their Lysis strategy, Q beta and the small DNA phage phi X174, effect host Lysis by targeting different enzymes in the multistep, universally conserved pathway of cell wall biosynthesis.