Design of specific inhibitors of quinolinate synthase based on [4Fe–4S] cluster coordination

Abstract

Quinolinate synthase (NadA) is a [4Fe–4S] cluster-containing enzyme involved in the formation of quinolinic acid, the precursor of the essential NAD coenzyme. Here, we report the synthesis and activity of derivatives of the first inhibitor of NadA. Using multidisciplinary approaches we have investigated their action mechanism and discovered additional specific inhibitors of this enzyme.