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 language | English |
|---|---|
| Pages (from-to) | 1236-1245 |
| Number of pages | 10 |
| Journal | Structure |
| Volume | 23 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 7 Jul 2015 |
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Crystal structures reveal that the reaction mechanism of imidazoleglycerol-phosphate dehydratase is controlled by switching Mn(II) coordination. / Bisson, Claudine; Britton, K. Linda; Sedelnikova, Svetlana E.; Rodgers, H. Fiona; Eadsforth, Thomas C.; Viner, Russell C.; Hawkes, Tim R.; Baker, Patrick J.; Rice, David W. (Lead / Corresponding author).
In: Structure, Vol. 23, No. 7, 07.07.2015, p. 1236-1245.Research output: Contribution to journal › Article
TY - JOUR
T1 - Crystal structures reveal that the reaction mechanism of imidazoleglycerol-phosphate dehydratase is controlled by switching Mn(II) coordination
AU - Bisson, Claudine
AU - Britton, K. Linda
AU - Sedelnikova, Svetlana E.
AU - Rodgers, H. Fiona
AU - Eadsforth, Thomas C.
AU - Viner, Russell C.
AU - Hawkes, Tim R.
AU - Baker, Patrick J.
AU - Rice, David W.
PY - 2015/7/7
Y1 - 2015/7/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84936847324&partnerID=8YFLogxK
U2 - 10.1016/j.str.2015.05.012
DO - 10.1016/j.str.2015.05.012
M3 - Article
C2 - 26095028
AN - SCOPUS:84936847324
VL - 23
SP - 1236
EP - 1245
JO - Structure
JF - Structure
SN - 0969-2126
IS - 7
ER -