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Quantum chemical modeling of the reaction path of chorismate mutase based on the experimental substrate/product complex

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journal contribution
posted on 10.05.2018, 11:36 by Daniel Burschowsky, Ute Krengel, Einar Uggerud, David Balcells
Chorismate mutase is a well‐known model enzyme, catalyzing the Claisen rearrangement of chorismate to prephenate. Recent high‐resolution crystal structures along the reaction coordinate of this enzyme enabled computational analyses at unprecedented detail. Using quantum chemical simulations, we investigated how the catalytic reaction mechanism is affected by electrostatic and hydrogen‐bond interactions. Our calculations showed that the transition state (TS) was mainly stabilized electrostatically, with Arg90 playing the leading role. The effect was augmented by selective hydrogen‐bond formation to the TS in the wild‐type enzyme, facilitated by a small‐scale local induced fit. We further identified a previously underappreciated water molecule, which separates the negative charges during the reaction. The analysis includes the wild‐type enzyme and a non‐natural enzyme variant, where the catalytic arginine was replaced with an isosteric citrulline residue.

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Citation

FEBS Open Bio , 2017, 7 (6), pp. 789-797

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Molecular & Cell Biology

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VoR (Version of Record)

Published in

FEBS Open Bio

Publisher

Wiley Open Access

issn

2211-5463

Acceptance date

22/03/2017

Copyright date

2017

Available date

10/05/2018

Publisher version

https://febs.onlinelibrary.wiley.com/doi/abs/10.1002/2211-5463.12224

Language

en

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