title: Crystal Structures of the Iron-Sulfur Cluster-Dependent Quinolinate Synthase in Complex with Dihydroxyacetone Phosphate, Iminoaspartate Analogues, and Quinolinate.
abstract: 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.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Fenwick
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Ealick
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004099:Dihydroxyacetone Phosphate / Q000737:chemistry; D007506:Iron-Sulfur Proteins / Q000737:chemistry; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry*; D011487:Protein Conformation; D043902:Pyrococcus horikoshii / Q000201:enzymology; D017378:Quinolinic Acid / Q000737:chemistry
chemical_list: D019843:Archaeal Proteins; D007506:Iron-Sulfur Proteins; D009097:Multienzyme Complexes; D001224:Aspartic Acid; C022512:quinolinic acid synthetase; D004099:Dihydroxyacetone Phosphate; C031948:iminoaspartic acid; D017378:Quinolinic Acid