Steve Ealick's Research Group
2-Amino-3,7-dideoxy-D-threo-hept-6-ulosonic Acid Synthase (ADHS)
2QJG, M. jannaschii ADHS complexed with fructose 1,6-bisphosphate
2QJH, M. jannaschii ADHS covalently bound to dihydroxyacetone phosphate
2QJI, M. jannaschii ADHS complexed with dihydroxyacetone phosphate and glycerol
Genes responsible for the generation of 3-dehydroquinate (DHQ), an early metabolite in the established shikimic pathway of the aromatic amino acid biosynthesis, are absent in most euryarchaeotes. Alternative gene products, Mj0400 and Mj1249, have been identified in Methanocaldococcus jannaschii as the enzymes involved in the synthesis of DHQ. 2-Amino-3,7-dideoxy-D-threo-hept-6-ulosonic acid (ADH) synthase , the product of the Mj0400 gene, catalyzes an transaldol reaction between 6-deoxy-5-ketofructose 1-phosphate and L-aspartate semialdehyde to yield ADH. The structure of ADH synthase (ADHS) was determined by molecular replacement using the structure of F16P aldolase from Thermoproteus tenax (TtFBPA) as a search model (PDB code: 1OJX). Based on the structural analysis and comparison of the enzyme with related aldolases, ADHS is classified as a new member of the class I aldolase superfamily.
The protomer of ADHS has a (βα)8-barrel fold). In addition to the core fold, the monomer contains four additional helices and a pair of β-strands. At the N-terminus, an additional helix a0 caps the barrel from the bottom. A pair of antiparallel β-strands found between β3 and α3 of the barrel is important for monomer interactions in the formation of the biological oligomer.
|In the crystal structure ADHS forms a decamer consisting of two doughnut shaped pentamers. Three different monomer-monomer interfaces are formed by the decamer and most of the contacts between the two pentamers are between monomers directly stacked with each contributing the same electrostatic interactions between charged residues and hydrophobic contacts.|
The active site of ADHS is at the top of the barrel as
shown by the crystal structure of ADHS in complex with fructose 1,6-bisphosphate.
The structure also indicates important catalytic residues that are conserved
in homologs of the enzyme.The ligand and the residues interacting with
the ligand are shown in ball-and-stick representation while dotted lines
indicate hydrogen bonds.
Morar M, White RH and Ealick SE. Structure of 2-Amino-3,7-dideoxy-D-threo-hept-6-ulosonic Acid Synthase, a Catalyst in a Novel Pathway for the Biosynthesis of Aromatic Amino Acids. Biochemistry 46:10562-10571(2007).