4p3x

Structure of the Fe4S4 quinolinate synthase NadA from Thermotoga maritima

spinqualitylabelsall models 4p3x, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4p3x is a 1 chain structure with sequence from Thermotoga maritima MSB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.65Å Ligands: MPD, SF4, ZN 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 Quinolinate synthase (NadA) is a Fe4S4 cluster-containing dehydrating enzyme involved in the synthesis of quinolinic acid (QA), the universal precursor of the essential nicotinamide adenine dinucleotide (NAD) coenzyme. A previously determined apo NadA crystal structure revealed the binding of one substrate analog, providing partial mechanistic information. Here, we report on the holo X-ray structure of NadA. The presence of the Fe4S4 cluster generates an internal tunnel and a cavity in which we have docked the last precursor to be dehydrated to form QA. We find that the only suitably placed residue to initiate this process is the conserved Tyr21. Furthermore, Tyr21 is close to a conserved Thr-His-Glu triad reminiscent of those found in proteases and other hydrolases. Our mutagenesis data show that all of these residues are essential for activity and strongly suggest that Tyr21 deprotonation, to form the reactive nucleophilic phenoxide anion, is mediated by the triad. NadA displays a dehydration mechanism significantly different from the one found in archetypical dehydratases such as aconitase, which use a serine residue deprotonated by an oxyanion hole. The X-ray structure of NadA will help us unveil its catalytic mechanism, the last step in the understanding of NAD biosynthesis. The Crystal Structure of FeS Quinolinate Synthase Unravels an Enzymatic Dehydration Mechanism That Uses Tyrosine and a Hydrolase-Type Triad.,Cherrier MV, Chan A, Darnault C, Reichmann D, Amara P, Ollagnier de Choudens S, Fontecilla-Camps JC J Am Chem Soc. 2014 Mar 26. PMID:24650327 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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