Aminodeoxychorismate synthase

Nonmenclature

This enzyme belongs to the class of transferases. This means that aminodeoxychorismate synthase catalyzes the transfer of one functional group from a molecule to another. Specifically, aminodeoxychorismate synthase is a transaminase that transfers an amino group to a keto acid. The systematic name is Chorismate:L-glutamine aminotransferase. Formerly aminodeoxychorismate synthase was referred to as PABA synthase; however this name is no longer recommended as it is understood that the formation of PABA requires the action of a further enzyme (4-amino-4-deoxychorismate lyase).

Common names that the enzyme goes by are:

• Aminodeoxychorismate synthase
• ADC synthase
• 4-amino-4-deoxychorismate synthase
• PabB

Reaction

In Escherichia coli, the reaction is a two step process. Glutamine amidotransferase (PabA) and 4-amino-4-deoxychorismate synthase (PabB) form a heterodimeric complex that catalyzes the synthesis of 4-amino-4-deoxychorismate. The first step occurs with PabA abstracting ammonia from glutamine. The second step occurs when PabB reacts both substrates (chorismate and ammonia) to synthesize 4-amino-4-deoxychorismate.

In plants such as Arabidopsis thaliana, aminodeoxychorismate synthase is a monomeric enzyme that carries out both steps of the reaction.

Structure

Aminodeoxychorismate synthase (PabB) is either a heterodimeric or monomeric enzyme depending on what organism it is from. The enzyme has 452-residues and consists of both alpha and beta folds that is very similar to some types of anthranilate synthase. The core of PabB consists of two domains that form a beta sandwich. Also, it has helices and loops around the outside of its core. The chorismate binding site on PabB consists of amino acids residues that make up beta sheet core and the two key alpha helices.

Certain aminodeoxychorismate synthase enzymes contain an additional binding site for tryptophan, thought to be a non-functional vestigial binding site. It is believed that aminodeoxychorismate synthase may have evolved from anthranilate synthase (TrpE) - an enzyme that catalyses the production of an intermediate on the path to tryptophan.

Homologues

Enzymes with similar structures to aminodeoxychorismate synthase are:

• Anthranilate synthase (TrpE)
• Isochorismate synthase (MenF)
• Salicylate synthase

A common feature among this list of enzymes is that they all utilize chorismate as a substrate.

Anti-folate drug target

Aminodeoxychorismate synthase is targeted by the antibiotics atrop-abyssomycin C and 6-fluoroshikimic acid. By inhibiting the production of an intermediate on the pathway to PABA, folate levels are depleted. Without sufficient folate, DNA and protein synthesis are severely impaired.

References

References

1. SAHR, Tobias. (May 15, 2006). "Folate synthesis in plants: purification, kinetic properties, and inhibition of aminodeoxychorismate synthase". Biochem. J..
2. Ye, Qi-Zhuang. (August 23, 1990). "p-Aminobenzoate synthesis in Escherichia coli: Purification and characterization of PabB as aminodeoxychorosmate synthase and enzyme X as aminodeoxychorismate lyase". Proc Natl Acad Sci USA.
3. Parsons, James. (November 21, 2001). "Structure of Escherichia coli Aminodeoxychorismate Synthase: Architectural Conservation and Diversity in Chorismate-Utilizing Enzymes". Biochemistry.
4. Bera, Asim. (December 21, 2013). "Structure of Aminodeoxychorismate Synthase from Stenotrophomonas maltophilia". Biochemistry.
5. (1991). "p-Aminobenzoate biosynthesis in Escherichia coli. Purification of aminodeoxychorismate lyase and cloning of pabC". J. Biol. Chem..
6. "ENZYME: 2.6.1.85". KEGG.