Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

anthranilate synthase By Reference

Anthranilate synthase catalyses the initial reaction in tryptophan biosynthesis in microorganisms and plants. This enzyme is one of a family of glutamine amidotransferases, enzymes that utilise the amide of glutamine in the biosynthesis of amino acids, nucleotides, coenzymes, and an amino sugar. Glutamine amidotransferases thus exert major role in utilisation of assimilated nitrogen. Anthranilate synthase is the most thoroughly characterised glutamine amidotransferase.

The enzyme from Serratia marcescens is a heterotetramer of anthranilate synthase (TrpE) and glutamine amidotransferase (TrpG) subunits both of which are required for function.




• Summary
• Step 1
• Step 2
• Step 3
• Step 4
• Step 5
• Step 6
• Products

In the TrpG subunit anthranilate synthase produces anthranilate from chorismate via transfer of an amino group, (generated from glutamine) using a catalytic triad of with well-known mechanism consisting of Cys84, His175, and Glu177. In the second AIDC lyase part of the reaction a standard second-order elimination can be invoked to yield the double bond between C2 and C3 with a histidine (H306) as the base abstracting the C2 proton and pyruvate as the leaving group. Mg(II) and water provide an assisting acid group.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Leu	Q06129	85	1qdl	85
Gly	Q06129	56	1qdl	56
His	Q06128	306	1qdl	307
Thr	Q06128	333	1qdl	334
Tyr	Q06128	357	1qdl	358
Arg	Q06128	377	1qdl	378
Cys	Q06129	84	1qdl	84
His	Q06129	175	1qdl	175
Gly	Q06128	393	1qdl	394
Glu	Q06129	177	1qdl	177

Step Components

overall reactant used, proton transfer, unimolecular elimination by the conjugate base, overall product formed, enzyme-substrate complex formation, bimolecular nucleophilic addition, intermediate formation, intermediate terminated, native state of enzyme regenerated, bimolecular elimination, deamination, intermediate collapse, enzyme-substrate complex cleavage



Step 1.

His175 deprotonates Cys84, activating it for a nucleophilic attack upon L-glutamine, forming an enzyme-substrate covalent bond.



Step 2.

The tetrahedral intermediate collapses, liberating ammonia, which deprotonates His175 and then passes to the other catalytic domain.



Step 3.

His175 deprotonates a water molecule, which initiates a nucleophilic attack on the Cys-bound intermediate.



Step 4.

The tetrahedral intermediate collapses, liberating Cys84, which deprotonates His175, and the glutamate product.



Step 5.

Ammiona acts as a nucleophile, adding to chorismate and eliminating water.



Step 6.

His306 deprotonates the C2 of the intermediate, eliminating the anthranilate product with concomitant deprotonation of the His306.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Citations

• In silico prediction of mutation sites for anthranilate synthase from Serratia marcesens to deregulate tryptophan feedback inhibition.
• Photoswitching of Feedback Inhibition by Tryptophan in Anthranilate Synthase.
• Structure of subunit I of the anthranilate synthase complex of Mycolicibacterium smegmatis.
• Effect of elicitors on the production of pyrroloquinazoline alkaloids by stimulating anthranilate synthase activity in Adhatoda vasica Nees cell cultures.
• The fused anthranilate synthase from Streptomyces venezuelae functions as a monomer.
• Uncoupling of an ammonia channel as a mechanism of allosteric inhibition in anthranilate synthase of Serratia marcescens: dynamic and graph theoretical analysis.
• Conversion of anthranilate synthase into isochorismate synthase: implications for the evolution of chorismate-utilizing enzymes.
• Still stable after 11 years: A Catharanthus roseus Hairy root line maintains inducible expression of anthranilate synthase.
• Structure and inhibition of subunit I of the anthranilate synthase complex of Mycobacterium tuberculosis and expression of the active complex.
• Microbial synthesis of the plant natural product precursor p-coumaric acid with Corynebacterium glutamicum.
• Examining the transcriptional response of overexpressing anthranilate synthase in the hairy roots of an important medicinal plant Catharanthus roseus by RNA-seq.