An insilico approach to structural elucidation of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Arabidopsis thaliana: hints for herbicide design

Abstract

3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHPS), the first enzyme of the shikimate pathway, is responsible for the synthesis of aromatic amino acids in microorganisms and plants. The pathway has been of increasing interest in the recent past as the enzymes are being targeted for antimicrobial drug and herbicide design. In the present work the three dimensional structure of the type II DAHPS present in Arabidopsis thaliana (At-DAHPS) is described and compared with type I DAHPS. The structure shows that the enzyme belongs to the (β/α)(8) TIM barrel family and that most of the active site residues are conserved in the type I DAHPS enzymes. Although the overall structures of the type I and type II enzymes are similar, there are differences in the extra barrel elements which may explain the different modes of enzyme regulation. At the N-terminus of At-DAHPS, there are three non-core helices, α0a (Ala72-Lys83), α0b (Ala94-Ala106) and α0c (Ala113-Val128), but no β(0), in contrast to the microbial type II DAHPS. Also, the (I/L)GAR motif in the type I DAHPS is substituted with xGxR in the case of type II DAHPS. Also, a motif NK(/I)PGR(/K) is present in the sequences of type II DAHPS including At-DAHPS. The elucidation of the active site architecture of At-DAHPS may provide a structural framework useful for the design of specific inhibitors towards herbicide development.