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Structure of the Y21F variant of quinolinate synthase in complex with PGHStructure of the Y21F variant of quinolinate synthase in complex with PGH
Structural highlights
Function[NADA_THEMA] Catalyzes the condensation of iminoaspartate with dihydroxyacetone phosphate to form quinolinate (By similarity). Publication Abstract from PubMedNadA 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. Crystallographic Trapping of Reaction Intermediates in Quinolinic Acid Synthesis by NadA.,Volbeda A, Saez Cabodevilla J, Darnault C, Gigarel O, Han TH, Renoux O, Hamelin O, Ollagnier-de-Choudens S, Amara P, Fontecilla-Camps JC ACS Chem Biol. 2018 Apr 19. doi: 10.1021/acschembio.7b01104. PMID:29641168[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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