1356109-26-6Relevant articles and documents
Crystallographic Trapping of Reaction Intermediates in Quinolinic Acid Synthesis by NadA
Volbeda, Anne,Saez Cabodevilla, Jaione,Darnault, Claudine,Gigarel, Océane,Han, Thi-Hong-Lien,Renoux, Oriane,Hamelin, Olivier,Ollagnier-De-Choudens, Sandrine,Amara, Patricia,Fontecilla-Camps, Juan C.
, p. 1209 - 1217 (2018)
NadA is a multifunctional enzyme that condenses dihydroxyacetone phosphate (DHAP) with iminoaspartate (IA) to generate quinolinic acid (QA), the universal precursor of the nicotinamide adenine dinucleotide (NAD(P)) cofactor. Using X-ray crystallography, we have (i) characterized two of the reaction intermediates of QA synthesis using a pH-shift approach and a slowly reacting Thermotoga maritima NadA variant and (ii) observed the QA product, resulting from the degradation of an intermediate analogue, bound close to the entrance of a long tunnel leading to the solvent medium. We have also used molecular docking to propose a condensation mechanism between DHAP and IA based on two previously published Pyrococcus horikoshi NadA structures. The combination of reported data and our new results provide a structure-based complete catalytic sequence of QA synthesis by NadA.
