Three sites and you are out: Ternary synergistic allostery controls aromatic amino acid biosynthesis in Mycobacterium tuberculosis.

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dc.contributor.authorBlackmore, N.J.
dc.contributor.authorReichau, S.
dc.contributor.authorJiao, W.
dc.contributor.authorHutton, R.D.
dc.contributor.authorBaker, E.N.
dc.contributor.authorJameson, G.B.
dc.contributor.authorParker, E.J.
dc.date.accessioned2016-07-22T03:18:58Z
dc.date.available2016-07-22T03:18:58Z
dc.date.issued2013en
dc.description.abstract3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first step in the shikimate pathway, the pathway responsible for the biosynthesis of the aromatic amino acids Trp, Phe, and Tyr. Unlike many other organisms that produce up to three isozymes, each feedback-regulated by one of the aromatic amino acid pathway end products, Mycobacterium tuberculosis expresses a single DAH7PS enzyme that can be controlled by combinations of aromatic amino acids. This study shows that the synergistic inhibition of this enzyme by a combination of Trp and Phe can be significantly augmented by the addition of Tyr.We used X-ray crystallography, mutagenesis, and isothermal titration calorimetry studies to show that DAH7PS from M. tuberculosis possesses a Tyr-selective site in addition to the Trp and Phe sites, revealing an unusual and highly sophisticated network of three synergistic allosteric sites on one enzyme. This ternary inhibitory response, by a combination of all three aromatic amino acids, allows a tunable response of the protein to changing metabolic demands.en
dc.identifier.citationBlackmore, N.J., Reichau, S., Jiao, W., Hutton, R.D., Baker, E.N., Jameson, G.B., Parker, E.J. (2013) Three sites and you are out: Ternary synergistic allostery controls aromatic amino acid biosynthesis in Mycobacterium tuberculosis.. Journal of Molecular Biology, 425(9), pp. 1582-92.en
dc.identifier.doihttps://doi.org/10.1016/j.jmb.2012.12.019
dc.identifier.urihttp://hdl.handle.net/10092/12493
dc.language.isoen
dc.publisherUniversity of Canterbury. Biomolecular Interaction Centreen
dc.rights.urihttps://hdl.handle.net/10092/17651
dc.subject.anzsrcField of Research::03 - Chemical Sciences::0304 - Medicinal and Biomolecular Chemistryen
dc.subject.anzsrcField of Research::11 - Medical and Health Sciencesen
dc.subject.anzsrcField of Research::06 - Biological Sciencesen
dc.titleThree sites and you are out: Ternary synergistic allostery controls aromatic amino acid biosynthesis in Mycobacterium tuberculosis.en
dc.typeJournal Article
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