5lqm

Structure of quinolinate synthase Y21F mutant in complex with citrate

spinqualitylabelsall models 5lqm, resolution 1.62Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5lqm is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FLC, SF4 Related: 4p3x Activity: Quinolinate synthase, with EC number 2.5.1.72 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [NADA_THEMA] Catalyzes the condensation of iminoaspartate with dihydroxyacetone phosphate to form quinolinate (By similarity). Publication Abstract from PubMed The enzyme NadA catalyzes the synthesis of quinolinic acid (QA), the precursor of the universal nicotinamide adenine dinucleotide (NAD) cofactor. Here, we report the crystal structures of complexes between the Thermotoga maritima (Tm) NadA K219R/Y107F variant and (i) the first intermediate (W) resulting from the condensation of dihydroxyacetone phosphate (DHAP) with iminoaspartate and (ii) the DHAP analogue and triose-phosphate isomerase inhibitor phosphoglycolohydroxamate (PGH). In addition, using the TmNadA K219R/Y21F variant, we have reacted substrates and obtained a crystalline complex between this protein and the QA product. We also show that citrate can bind to both TmNadA K219R and its Y21F variant. The W structure indicates that condensation causes dephosphorylation. We propose that catalysis by the K219R/Y107F variant is arrested at the W intermediate because the mutated protein is unable to catalyze its aldo-keto isomerization and/or cyclization that ultimately lead to QA formation. Intriguingly, PGH binds to NadA with its phosphate group at the site where the carboxylate groups of W also bind. Our results shed significant light on the mechanism of the reaction catalyzed by NadA. Crystal Structures of Quinolinate Synthase in Complex with a Substrate Analogue, the Condensation Intermediate, and Substrate-Derived Product.,Volbeda A, Darnault C, Renoux O, Reichmann D, Amara P, Ollagnier de Choudens S, Fontecilla-Camps JC J Am Chem Soc. 2016 Aug 30. PMID:27545412 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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