Anthranilate synthase

Anthranilate synthase creates anthranilate, an important intermediate in the biosynthesis of indole, and by extension, the amino acid tryptophan. Tryptophan can then be metabolized further into serotonin, melatonin, or various auxins.

Anthranilate synthase catalyzes the change from chorismate to anthranilate. As its other substrate, it can use either glutamine or ammonia.{{Cite journal|last1=Tamir|first1=H.|last2=Srinivasan|first2=P. R.|date=June 1970|title=Studies of the Mechanism of Anthranilate Synthase Reaction|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=66|issue=2|pages=547–551|doi=10.1073/pnas.66.2.547|issn=0027-8424|pmid=5271179|pmc=283079|bibcode=1970PNAS...66..547T|doi-access=free}} During the reaction, both a hydroxyl group and an enolpyruvyl group are removed from the aromatic ring. The enolpyruvyl group gains a proton to form pyruvate. It has been shown that the proton comes from the surrounding water and not from an intramolecular shift of a hydrogen atom on the substrates. The amino group of glutamine (or ammonia itself) attacks chorismate in position 2, which leads to{{how|date=January 2022}} the elimination of enolpyruvyl group from position 3. In the process, an aromatic ring is re-formed.

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The complex is made up of α and β subunits. Gel filtration experiments reveal that the complex occurs as an α₂β₂ tetramer under native conditions, and as an αβ dimer under high salt concentrations.{{cite journal|last1=Poulsen|first1=C|last2=Bongaerts|first2=RJ|last3=Verpoorte|first3=R|title=urification and characterization of anthranilate synthase from Catharanthus roseus|journal=European Journal of Biochemistry|date=March 1993|volume=212|issue=2|pages=431–440|pmid=8444181|doi=10.1111/j.1432-1033.1993.tb17679.x|doi-access=free}} The αβ dimers interact through the α subunits to form the complex.

The subunits of anthranilate synthase are encoded by the trpE and trpD genes in E. coli, both of which appear in the trp operon.

In Enterobacteriaceae, this enzyme exists in the form of an aggregate with anthranilate phosphoribosyltransferase. If these two enzymes are not clustered, the complex is unable to use glutamine as a substrate and can only use ammonia.

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This enzyme belongs to the family of lyases, to be specific the oxo-acid-lyases, which cleave carbon-carbon bonds. The systematic name of this enzyme class is chorismate pyruvate-lyase (amino-accepting; anthranilate-forming). Other names in common use include anthranilate synthetase, chorismate lyase, and chorismate pyruvate-lyase (amino-accepting). This enzyme participates in phenylalanine, tyrosine and tryptophan biosynthesis and two-component system - general.

As of late 2007, five structures have been solved for this class of enzymes, with PDB accession codes {{PDB link|1I1Q}}, {{PDB link|1I7Q}}, {{PDB link|1I7S}}, {{PDB link|1QDL}}, and {{PDB link|2I6Y}}.

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{{reflist|1}}

• {{cite journal |vauthors=Baker TI, Crawford IP | year = 1966 | title = Anthranilate synthetase. Partial purification and some kinetic studies on the enzyme from Escherichia coli | journal = J. Biol. Chem. | volume = 241 | pages = 5577–5584 | pmid = 5333199 | issue = 23 | doi = 10.1016/S0021-9258(18)96383-0 | doi-access = free }}
• {{cite book |vauthors=Creighton TE, Yanofsky C | year = 1970 | title = Chorismate to tryptophan (Escherichia coli) - Anthranilate synthetase, PR transferase, PRA isomerase, InGP synthetase, tryptophan synthetase | chapter = Chorismate to tryptophan (Escherichia coli)—anthranilate synthetase, PR transferase, PRA isomerase, InGP synthetase, tryptophan synthetase | series = Methods Enzymol. | volume = 17A | pages = 365–380 | doi=10.1016/0076-6879(71)17215-1| isbn = 978-0-12-181874-6 }}
• {{cite journal |vauthors=Kung CC, Huang WN, Huang YC, Yeh KC | year = 2006 | title = Proteomic survey of copper-binding proteins in Arabidopsis roots by immobilized metal affinity chromatography and mass spectrometry | journal = Proteomics | volume = 6 | pages = 2746–2758 | pmid = 16526091 | doi = 10.1002/pmic.200500108 | issue = 9 | s2cid = 25896917 }}
• {{cite journal |vauthors=Ito J, Yanofsky C | year = 1969 | title = Anthranilate synthetase, an enzyme specified by the tryptophan operon of Escherichia coli: Comparative studies on the complex and the subunits | journal = J. Bacteriol. | volume = 97 | pages = 734–742 | pmid = 4886290 | issue = 2 | doi = 10.1128/JB.97.2.734-742.1969 | pmc = 249753 }}
• {{cite journal |vauthors=Zalkin H, Kling D | year = 1968 | title = Anthranilate synthetase. Purification and properties of component I from Salmonella typhimurium | journal = Biochemistry | volume = 7 | pages = 3566–3573 | pmid = 4878701 | doi = 10.1021/bi00850a034 | issue = 10 }}

{{Carbon-carbon lyases}}

{{Enzymes}}

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Category:EC 4.1.3

Category:Enzymes of known structure

Category:Anthranilates

{{4.1-enzyme-stub}}