Fingerprinting differential active site constraints of ATPases

Hacker, Stephan M.; Hardt, Normann; Buntru, Alexander; Pagliarini, Dana; Möckel, Martin M.; Mayer, Thomas U.; Scheffner, Martin; Hauck, Christof R.; Marx, Andreas

Fingerprinting differential active site constraints of ATPases

Dateien

Mayer216893.pdfGröße: 5.15 MBDownloads: 869

Datum

2013

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Chemie
Zukunftskolleg

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Chemical Science. 2013, 4(4), pp. 1588-1596. ISSN 2041-6520. eISSN 2041-6539. Available under: doi: 10.1039/C3SC21916J

Zusammenfassung

The free energy provided by adenosine triphosphate (ATP) hydrolysis is central to many cellular processes and, therefore, the number of enzymes utilizing ATP as a substrate is almost innumerable. Modified analogues of ATP are a valuable means to understand the biological function of ATPases. Although these enzymes have evolved towards binding to ATP, large differences in active site architectures were found. In order to systematically access the specific active site constraints of different ATPases suitable tools are required. Here, we present the synthesis of six new ATP-based ATPase probes modified at three different positions of the nucleobase and the ribose, respectively. Subsequently, we studied the ATPases focal adhesion kinase FAK, the ubiquitin-activating protein UBA1 and the kinesin Eg5 as examples for ATPases that process ATP by different mechanisms. We find that for each of these enzymes at least one position in ATP can be modified without loss of acceptance by the enzyme. However, the positions at which modifications are tolerated significantly differ between the studied enzymes allowing fingerprints to be drawn for reactivity. The introduced ATP analogues may form the basis for the design of tailored probes with increased affinity and specificity for a specific ATPase of interest.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

HACKER, Stephan M., Normann HARDT, Alexander BUNTRU, Dana PAGLIARINI, Martin M. MÖCKEL, Thomas U. MAYER, Martin SCHEFFNER, Christof R. HAUCK, Andreas MARX, 2013. Fingerprinting differential active site constraints of ATPases. In: Chemical Science. 2013, 4(4), pp. 1588-1596. ISSN 2041-6520. eISSN 2041-6539. Available under: doi: 10.1039/C3SC21916J

BibTex

@article{Hacker2013Finge-21689,
  year={2013},
  doi={10.1039/C3SC21916J},
  title={Fingerprinting differential active site constraints of ATPases},
  number={4},
  volume={4},
  issn={2041-6520},
  journal={Chemical Science},
  pages={1588--1596},
  author={Hacker, Stephan M. and Hardt, Normann and Buntru, Alexander and Pagliarini, Dana and Möckel, Martin M. and Mayer, Thomas U. and Scheffner, Martin and Hauck, Christof R. and Marx, Andreas}
}

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