PROSITE documentation PDOC52061

DAHPS class-I and -II core TIM-barrel domains profiles

Despite their different biosynthetic roles in microorganisms and plants, the enzymes 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS) and 3-deoxy-D-manno-octulosonate-8-phosphate synthase (KDOPS) possess significant mechanistic and structural similarities. DAHPS catalyzes the first step in the biosynthesis of the aromatic amino acids as well as other aromatic compounds of primary and secondary metabolism, the aldol-like condensation of phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P) with the formation of DAHP and phosphate. KDOPS catalyses the first step in the biosynthesis of a variety of cell surface components, an analogous condensation of PEP and D-arabinose-5-phosphate (A5P), which is one carbon atom longer than E4P, with the formation of KDOP and phosphate. DAHPS and KDOPS are unusual in that they both cleave the C-O, not the O-P, bond of PEP. Members of both enzymes were divided into two distinct main families (defined as class-I and class-II). The class-I family is found mostly in prokaryotic and archaeal organisms. However, some eukaryotic examples have been identified, e.g., in Saccharomyces cerevisiae and Neurospora crassa. This type of DAHPS can be further divided into subfamilies Iα and Iβ. KDOPSs have been assigned to the Iβ subfamily. The class-II, defined as "plant-like" DAHPS, consists of enzymes from higher plants together with a group of microbial enzymes that function mainly in pathways of secondary metabolism [1,2,3,4,5].

Although there is no significant sequence similarity between the class-II DAHPSs and the class-I DAHPSs and KDOPSs, they share a characteristic (β/ α)8 TIM-barrel fold in which the eight parallel β-strands are each followed by α-helices, and similar active site architecture (see <PDB:1OFQ>, <PDB:1ZCO>, <PDB:1D9E>) and <PDB:2B7O>) [1,2,3,4,5].

We developed two profiles for the DAHPS core TIM-barrel domain, one for the class-I and one for the class-II.