In enzymology, an aminodeoxychorismate synthase
EC 2.6.1.85
is an enzyme that catalyzes the chemical reaction :

chorismate Chorismic acid, more commonly known as its anionic form chorismate, is an important biochemical intermediate in plants and microorganisms. It is a precursor for: * The aromatic amino acids phenylalanine, tryptophan, and tyrosine * Indole, indole d ...

L-glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, ...

\rightleftharpoons

4-amino-4-deoxychorismate +

L-glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...

Thus, the two substrates of this enzyme are

and

, whereas its two

products Product may refer to: Business * Product (business), an item that serves as a solution to a specific consumer problem. * Product (project management), a deliverable or set of deliverables that contribute to a business solution Mathematics * Produ ...

are 4-amino-4-deoxychorismate and

. It is part of a pathway for the biosynthesis of ''para''-aminobenzoic acid (PABA); a precursor for the production of folates. Folates are family of

cofactors Cofactor may also refer to: * Cofactor (biochemistry), a substance that needs to be present in addition to an enzyme for a certain reaction to be catalysed * A domain parameter in elliptic curve cryptography, defined as the ratio between the order ...

that are essential for living organisms. Folate cofactors are used in several one-carbon transfer reactions required during the synthesis of essential metabolites, including

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...

and

thymidylate Thymidine monophosphate (TMP), also known as thymidylic acid (conjugate base thymidylate), deoxythymidine monophosphate (dTMP), or deoxythymidylic acid (conjugate base deoxythymidylate), is a nucleotide that is used as a monomer in DNA. It is an ...

. Aminodeoxychorismate synthase (PabB), a 51 kDa protein in ''

E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

'', is encoded by the gene ''pabB''. 4-amino-4-deoxychorismate, the product of PabB, can be converted to ''para''-aminobenzoic acid by the enzyme 4-amino-4-deoxychorismate lyase (PabC).

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 A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature. A semisystematic name or semitrivial ...

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 certain microbial species such as ''Escherichia coli, ''aminodeoxychorismate synthase is a heterodimeric complex composed of two proteins, glutamine amidotransferase (PabA) and 4-amino-4-deoxychorismate synthase (PabB). In other species such as plants or lower eukaryotes an enzyme comprising a single polypeptide performs both reactions. 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 Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...

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 ''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant native to Eurasia and Africa. ''A. thaliana'' is considered a weed; it is found along the shoulders of roads and in disturbed land. A winter a ...

'', 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 Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α- carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

, 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 The enzyme anthranilate synthase () catalyzes the chemical reaction :chorismate + L-glutamine \rightleftharpoons anthranilate + pyruvate + L-glutamate Function Anthranilate synthase creates anthranilate, an important intermediate in the biosynthe ...

(TrpE) * Isochorismate synthase (MenF) *

Salicylate synthase Salicylate synthase is an enzyme that catalyzes the chemical reaction: :chorismate → salicylic acid MbtI is the responsible enzyme from ''Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria ...

A common feature among this list of enzymes is that they all utilize

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

* * {{Portal bar, Biology, border=no EC 2.6.1 Enzymes of unknown structure