Crystal Structures of the Iron-Sulfur Cluster-Dependent Quinolinate Synthase in Complex with Dihydroxyacetone Phosphate, Iminoaspartate Analogues, and Quinolinate.

Publication Type:

Journal Article


Biochemistry, Volume 55, Issue 30, p.4135-9 (2016)


Archaeal Proteins, Aspartic Acid, Catalytic Domain, Crystallography, X-Ray, Dihydroxyacetone Phosphate, Iron-Sulfur Proteins, Models, Molecular, Multienzyme Complexes, Protein Conformation, Pyrococcus horikoshii, Quinolinic Acid


<p>The quinolinate synthase of prokaryotes and photosynthetic eukaryotes, NadA, contains a [4Fe-4S] cluster with unknown function. We report crystal structures of Pyrococcus horikoshii NadA in complex with dihydroxyacetone phosphate (DHAP), iminoaspartate analogues, and quinolinate. DHAP adopts a nearly planar conformation and chelates the [4Fe-4S] cluster via its keto and hydroxyl groups. The active site architecture suggests that the cluster acts as a Lewis acid in enediolate formation, like zinc in class II aldolases. The DHAP and putative iminoaspartate structures suggest a model for a condensed intermediate. The ensemble of structures suggests a two-state system, which may be exploited in early steps.</p>

PhNadA (5KTM), PhNadA/DHAP (5KTN), PhNadA/quinolinate (5KTO), PhNadA/itaconate (5KTP), PhNa-dA/maleate (5KTR), PhNadA/citraconate (5KTS), and PhNadA/L- malate (5KTT)