Crystallographic Trapping of Reaction Intermediates in Quinolinic Acid Synthesis by NadA. - Archive ouverte HAL Access content directly
Journal Articles ACS Chemical Biology Year : 2018

Crystallographic Trapping of Reaction Intermediates in Quinolinic Acid Synthesis by NadA.

Abstract

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 analog, 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.
Not file

Dates and versions

hal-01771643 , version 1 (19-04-2018)

Identifiers

Cite

Anne Volbeda, Cabodevilla Jaione Saez, Claudine Darnault, Océane Gigarel, Thi-Hong-Lien Han, et al.. Crystallographic Trapping of Reaction Intermediates in Quinolinic Acid Synthesis by NadA.. ACS Chemical Biology, 2018, 13 (5), pp.1209-1217. ⟨10.1021/acschembio.7b01104⟩. ⟨hal-01771643⟩
103 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More