Studies of inhibitor binding to the [4Fe-4S] cluster of quinolinate synthase.

Alice Chan (1) , Martin Clémancey (1) , Jean-Marie Mouesca (2) , Patricia Amara (3) , Olivier Hamelin (1) , Jean-Marc Latour (1) , Sandrine Ollagnier de Choudens (1)

1 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux
2 RM - Magnetic Resonance
3 IBS - UMR 5075 - Institut de biologie structurale

Stop for NadA! A [4Fe-4S] enzyme, NadA, catalyzes the formation of quinolinic acid in de novo nicotinamide adenine dinucleotide (NAD) biosynthesis. A structural analogue of an intermediate, 4,5-dithiohydroxyphthalic acid (DTHPA), has an in vivo NAD biosynthesis inhibiting activity in E. coli. The inhibitory effect can be explained by the coordination of DTHPA thiolate groups to a unique Fe site of the NadA [4Fe-4S] cluster.

Domaines: Biochimie, Biologie Moléculaire

Alice Chan, Martin Clémancey, Jean-Marie Mouesca, Patricia Amara, Olivier Hamelin, et al.. Studies of inhibitor binding to the [4Fe-4S] cluster of quinolinate synthase.. Angewandte Chemie International Edition, 2012, 51 (31), pp.7711-4. ⟨10.1002/anie.201202261⟩. ⟨hal-01054373⟩