Dynamic control of the prolyl isomerase function of the dual-domain SlyD protein

Kovermann, Michael; Balbach, Jochen

Dynamic control of the prolyl isomerase function of the dual-domain SlyD protein

Files

Kovermann_2-65gn5jvh7f633.PDF(1.08 MB)

Date

2013

Authors

Kovermann, Michael

Balbach, Jochen

Publication type

Journal article

Publication status

Published

Published in

Biophysical Chemistry ; 171 (2013). - pp. 16-23. - ISSN 0301-4622. - eISSN 1873-4200

Abstract

Local dynamics on variable timescales are important to facilitate high catalytic efficiency in enzymes. In this study, we examined the dual-domain peptidyl-prolyl cis/trans-isomerase (PPIase) SlyD with regard to its catalytic cycle. Fluorescence- and NMR-based experiments were performed to understand the high catalytic efficiency of SlyD compared to single domain FKBP proteins. We probed local conformational changes for amino acids involved in substrate-binding (IF domain) and substrate-catalysis (FKBP domain) taking place on the timescale of substrate turnover. Binding of the PPIase activity inhibitors to the FKBP domain suppressed the conformational freedom of the remote IF domain. A single side-chain mutation in the active site strongly reduced the rate of substrate turnover and changed the conformational dynamics of all amino acids involved in catalysis. This dynamic interplay between substrate-binding domain and PPIase domain determines the high catalytic activity of SlyD and inhibitor-binding modulates the backbone plasticity required for enzyme activity.

Subject (DDC)

540 Chemistry

Keywords

NMR, Fluorescence, PPIase, FKBP, Dynamics, Enzymology

Cite This

ISO 690

KOVERMANN, Michael, Jochen BALBACH, 2013. Dynamic control of the prolyl isomerase function of the dual-domain SlyD protein. In: Biophysical Chemistry. 171, pp. 16-23. ISSN 0301-4622. eISSN 1873-4200. Available under: doi: 10.1016/j.bpc.2012.11.003

BibTex

@article{Kovermann2013-01Dynam-44410,
  year={2013},
  doi={10.1016/j.bpc.2012.11.003},
  title={Dynamic control of the prolyl isomerase function of the dual-domain SlyD protein},
  volume={171},
  issn={0301-4622},
  journal={Biophysical Chemistry},
  pages={16--23},
  author={Kovermann, Michael and Balbach, Jochen}
}

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Bibliography of Konstanz

No

Refereed

Yes