InterPro: IPR006219 DHAP synthase, class 1

Members of this group catalyze the first enzymatic reaction of the shikimate pathway. The common (shikimate) pathway links metabolism of carbohydrates to biosynthesis of aromatic amino acids phenylalanine, tyrosine, tryptophan, and derivatives in microorganisms and in plants. In a sequence of seven enzymatic reactions, D-erythrose 4-phosphate (E4P), an intermediate of the pentose phosphate pathway, and phosphoenol pyruvate (PEP), a glycolytic intermediate, are converted to chorismate. The pathway begins with the stereospecific condensation of E4P and PEP to yield 7-phospho 2-dehydro 3-deoxy-D-arabino-heptulosonate (DAHP), catalyzed by 3-deoxy-7-phosphoheptulonate synthase (DAHPS) (EC:2.5.1.54). The divalent metal cation requirement of this enzyme can be satisfied by a broad range of metals [1]. A Cys residue in a Cys-X-X-His motif has been identified as part of a metal binding site [2]. In Escherichia coli, the enzyme exists in three isoforms, each specifically inhibited by one of the three aromatic amino acids.

DAHP synthetases fall into two classes, class I (represented by this entry) and class II (represented by PIRSF015573). Class I was believed to be limited to microorganisms and class II to plants. However, a more recent study showed that class II also contains enzymes from a microbial eukaryote and several bacteria [3]. Brick and Woodard [4] proposed that the difference between the two classes lies in their metal ion requirement for activity. Whereas class I requires no metal cation, class II is dependent on a metal cation for activity. However, recently a class I DAHP synthase from Thermotoga maritima has been purified, characterised, and shown to be a metalloenzyme [5].

The three-dimentional structures of DAHP synthases have been determined [6, 7, 8, 9, 10]. The DAHPS(Phe) monomer is a (beta/alpha)8 barrel with an additional N-terminal beta strand and helices and an extra beta sheet near the C terminus [10]. The active site is located in a cleft at the carboxyl end of the barrel [9]. The allosteric feedback inhibition binding site of DAHPS(Phe) is composed of residues from two adjacent subunits of a tight dimer and is at least 20 angstroms away from the closest active site [8].

The absence of the shikimate pathway in animals makes it an attractive target for nontoxic herbicidal, antimicrobial, and antifungal agents. The nontoxic herbicide glyphosphate competitively inhibits 3-phosphoshikimate 1-carboxyvinyltransferase, the sixth enzymatic reaction of the pathway.