Challenging a decades-old paradigm: ProB and ProA do not channel the unstable intermediate in proline synthesis after all

The pathway for synthesis of proline in most forms of life produces a highly unstable intermediate, γ-L-glutamyl 5-phosphate (GP). For nearly 70 y, channeling of this intermediate from the active site of glutamate 5-kinase to the active site of GP reductase has been believed to protect GP from cyclization to a dead-end product. However, the evidence presented in support of this idea is not conclusive. We show that changes in the structures of the kinase or reductase that should preclude a protein-protein interaction do not compromise proline synthesis in