Studies of inhibitor binding to the [4Fe-4S] cluster of quinolinate synthase.
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.
Laboratoire de Chimie de Biologie des Métaux, UMR 5249, Université Joseph Fourier, Grenoble-1, CNRS-CEA 17, Rue des Martyrs, 38054 Grenoble Cedex 9, France.
Alice
A
Chan
Martin
M
Clémancey
Jean-Marie
JM
Mouesca
Patricia
P
Amara
Olivier
O
Hamelin
Jean-Marc
JM
Latour
Sandrine
S
Ollagnier de Choudens
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D004099:Dihydroxyacetone Phosphate / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D007506:Iron-Sulfur Proteins; D004099:Dihydroxyacetone Phosphate; D019883:Alkyl and Aryl Transferases; C532144:quinolinate synthase, E coli