Crystal structures reveal that the reaction mechanism of imidazoleglycerol-phosphate dehydratase is controlled by switching Mn(II) coordination

Claudine Bisson, K. Linda Britton, Svetlana E. Sedelnikova, H. Fiona Rodgers, Thomas C. Eadsforth, Russell C. Viner, Tim R. Hawkes, Patrick J. Baker, David W. Rice (Lead / Corresponding author)

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Abstract

Summary Imidazoleglycerol-phosphate dehydratase (IGPD) catalyzes the Mn(II)-dependent dehydration of imidazoleglycerol phosphate (IGP) to 3-(1H-imidazol-4-yl)-2-oxopropyl dihydrogen phosphate during biosynthesis of histidine. As part of a program of herbicide design, we have determined a series of high-resolution crystal structures of an inactive mutant of IGPD2 from Arabidopsis thaliana in complex with IGP. The structures represent snapshots of the enzyme trapped at different stages of the catalytic cycle and show how substrate binding triggers a switch in the coordination state of an active site Mn(II) between six- and five-coordinate species. This switch is critical to prime the active site for catalysis, by facilitating the formation of a high-energy imidazolate intermediate. This work not only provides evidence for the molecular processes that dominate catalysis in IGPD, but also describes how the manipulation of metal coordination can be linked to discrete steps in catalysis, demonstrating one way that metalloenzymes exploit the unique properties of metal ions to diversify their chemistry.

Original languageEnglish
Pages (from-to)1236-1245
Number of pages10
JournalStructure
Volume23
Issue number7
DOIs
Publication statusPublished - 7 Jul 2015

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    Bisson, C., Britton, K. L., Sedelnikova, S. E., Rodgers, H. F., Eadsforth, T. C., Viner, R. C., Hawkes, T. R., Baker, P. J., & Rice, D. W. (2015). Crystal structures reveal that the reaction mechanism of imidazoleglycerol-phosphate dehydratase is controlled by switching Mn(II) coordination. Structure, 23(7), 1236-1245. https://doi.org/10.1016/j.str.2015.05.012