Steve Ealick's Research Group

Pyrococcus furiosus Quinolinate Synthase

PDB file:

4HHE (replaces 2QS0)


Pyrococcus furiosus quinolinate synthase (PfQS) catalyzes the condensation of iminoaspartate and dihydroxyacetone phosphate to form quinolinate, the universal precursor in the de novo biosynthesis of nicotinamide adenine dinucleotide (NAD). The structure was solved using single anomalous dispersion methods and compared to that of Pyrococcus horikoshii quinolinate synthase (PhQS; PDB =1WZU).

The monomer consists of three domains each of which have the similar topology.The three domains are connected by flexible linkers, with each of the linkers containing a Cys residue that is conserved among all QS proteins.


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PfQS forms a dimer related by 2-fold symmetry in the unit cell The dimer interface is formed by domain 2, the connection between domain 2 and 3, and the connection between domain 3 and the C-terminal α-helices. This formation leaves domain 3 completely exposed to the solvent.

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The malate molecule from the PhQS crystal structure was used as a guide to position a model of the final intermediate, 5-hydroxy-4,5-dihydroquinolinate in PfQS. Also shown is the iron-sulfur cluster.

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Soriano EV, Zhang Y, Colabroy K, Sanders JM, Settembre EC, Dorrestein PC, Begley TP, and Ealick SE. Active Site Models for Complexes of Quinolinate Synthase with Substrates and Intermediates. Acta Crystallogr. D. 69:1685–1696 (2013).

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