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

Biochemistry. 2016 Aug 2;55(30):4135-9. doi: 10.1021/acs.biochem.6b00626. Epub 2016 Jul 22.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Archaeal Proteins / chemistry*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / chemistry
  • Catalytic Domain
  • Crystallography, X-Ray
  • Dihydroxyacetone Phosphate / chemistry
  • Iron-Sulfur Proteins / chemistry
  • Models, Molecular
  • Multienzyme Complexes / chemistry*
  • Protein Conformation
  • Pyrococcus horikoshii / enzymology
  • Quinolinic Acid / chemistry

Substances

  • Archaeal Proteins
  • Iron-Sulfur Proteins
  • Multienzyme Complexes
  • Aspartic Acid
  • quinolinic acid synthetase
  • Dihydroxyacetone Phosphate
  • iminoaspartic acid
  • Quinolinic Acid