Structural basis for catalytically restrictive dynamics of a high-energy enzyme state

Kovermann, Michael; Ådén, Jörgen; Grundström, Christin; Sauer-Eriksson, A. Elisabeth; Sauer, Uwe H.; Wolf-Watz, Magnus

Structural basis for catalytically restrictive dynamics of a high-energy enzyme state

Files

Kovermann_0-414063.pdf(871.21 KB)

Date

2015

Authors

Kovermann, Michael

Ådén, Jörgen

Grundström, Christin

Sauer-Eriksson, A. Elisabeth

Sauer, Uwe H.

Wolf-Watz, Magnus

Publication type

Journal article

Publication status

Published

Published in

Nature Communications ; 6 (2015). - 7644. - eISSN 2041-1723

Abstract

An emerging paradigm in enzymology is that transient high-energy structural states play crucial roles in enzymatic reaction cycles. Generally, these high-energy or 'invisible' states cannot be studied directly at atomic resolution using existing structural and spectroscopic techniques owing to their low populations or short residence times. Here we report the direct NMR-based detection of the molecular topology and conformational dynamics of a catalytically indispensable high-energy state of an adenylate kinase variant. On the basis of matching energy barriers for conformational dynamics and catalytic turnover, it was found that the enzyme's catalytic activity is governed by its dynamic interconversion between the high-energy state and a ground state structure that was determined by X-ray crystallography. Our results show that it is possible to rationally tune enzymes' conformational dynamics and hence their catalytic power--a key aspect in rational design of enzymes catalysing novel reactions.

Subject (DDC)

540 Chemistry

Cite This

ISO 690

KOVERMANN, Michael, Jörgen ÅDÉN, Christin GRUNDSTRÖM, A. Elisabeth SAUER-ERIKSSON, Uwe H. SAUER, Magnus WOLF-WATZ, 2015. Structural basis for catalytically restrictive dynamics of a high-energy enzyme state. In: Nature Communications. 6, 7644. eISSN 2041-1723. Available under: doi: 10.1038/ncomms8644

BibTex

@article{Kovermann2015-07-03Struc-39480,
  year={2015},
  doi={10.1038/ncomms8644},
  title={Structural basis for catalytically restrictive dynamics of a high-energy enzyme state},
  volume={6},
  journal={Nature Communications},
  author={Kovermann, Michael and Ådén, Jörgen and Grundström, Christin and Sauer-Eriksson, A. Elisabeth and Sauer, Uwe H. and Wolf-Watz, Magnus},
  note={Article Number: 7644}
}

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