DAHP synthase

DAHP Synthase (3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase) is an enzyme that catalyzes the first step in the shikimate pathway, which is involved in the biosynthesis of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) in microorganisms and plants. This pathway is not found in animals, making it an interesting target for the development of antibiotics, herbicides, and other agents. DAHP Synthase combines phosphoenolpyruvate (PEP) and erythrose-4-phosphate (E4P) to form 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP).

Function

The shikimate pathway is crucial for the biosynthesis of essential aromatic compounds in plants and microorganisms. DAHP Synthase, as the initial enzyme in this pathway, plays a pivotal role in controlling the flow of carbon into the pathway and thus the production of aromatic amino acids. These amino acids are precursors to many secondary metabolites with diverse functions in biological systems, including hormones, alkaloids, and phenolics.

Structure

DAHP Synthase is a protein that can exist in multiple isoforms, which are encoded by different genes. These isoforms may be regulated differently across species and even within different tissues of the same organism, allowing for a fine-tuned control of aromatic amino acid biosynthesis. The enzyme's structure has been studied extensively, revealing a catalytic site where the substrates PEP and E4P bind and undergo a condensation reaction to form DAHP.

Mechanism

The enzymatic action of DAHP Synthase involves the condensation of PEP and E4P through a series of steps that include the formation of an enolpyruvyl adduct, followed by a rearrangement and dehydration to produce DAHP. This reaction is dependent on divalent cations, such as Mg2+ or Mn2+, as cofactors for activity.

Regulation

The activity of DAHP Synthase is subject to feedback inhibition by the end products of the shikimate pathway, namely the aromatic amino acids. This feedback inhibition ensures that the production of these essential compounds is tightly regulated according to the cell's metabolic needs. Additionally, the expression of DAHP Synthase genes can be regulated at the transcriptional level in response to environmental cues and developmental signals.

Clinical Significance

Given its absence in animals, the shikimate pathway, and specifically DAHP Synthase, presents an attractive target for the development of antimicrobial agents and herbicides. Inhibitors of DAHP Synthase can potentially block the synthesis of aromatic amino acids in pathogens, leading to their death, without affecting the host organism.

See Also

• Shikimate pathway
• Aromatic amino acids
• Enzyme inhibition
• Antibiotics
• Herbicides

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External Links

• Example of DAHP Synthase sequence in NCBI Protein Database

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  DAHP_synthase

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  DAHP Synthase Active Site Residues and DAHP oxime

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  DAHP Oxime in DAHP synthase Active Site

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  DAHP synthase reaction

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  DAHP synthase quaternary structure

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  DAHP synthase cartoon quaternary structure