Fe₄S₄‐Quinolinate Synthase (NadA)

Abstract

Quinolinate synthase is the second enzyme in the nicotinamide adenine dinucleotide (NAD) synthetic de novo pathway I. The enzyme reacts iminoaspartate with dihydroxylaceton phosphate to form the universal NAD precursor quinolinic acid. Iminoaspartate is made from l ‐aspartate by aspartate oxidase in many prokaryotes such as Escherichia coli , and by aspartate dehydrogenase in Archaea and hyperthermophilic bacteria. Quinolinate synthase is a fascinating multifunctional enzyme capable of catalyzing a TIM‐like isomerization, a dephosphorylation‐coupled condensation, and two dehydrations. All these reactions appear to take place in a relative small cavity facing the Fe 4 S 4 cluster at the end of a protein tunnel that gets obstructed by their binding.