These authors contributed equally to this work.
Development of Selective RabGGTase Inhibitors and Crystal Structure of a RabGGTase–Inhibitor Complex†
Article first published online: 10 APR 2008
Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 47, Issue 20, pages 3747–3750, May 5, 2008
How to Cite
Guo, Z., Wu, Y.-W., Tan, K.-T., Bon, Robin S., Guiu-Rozas, E., Delon, C., Nguyen, Uyen T., Wetzel, S., Arndt, S., Goody, Roger S., Blankenfeldt, W., Alexandrov, K. and Waldmann, H. (2008), Development of Selective RabGGTase Inhibitors and Crystal Structure of a RabGGTase–Inhibitor Complex. Angew. Chem. Int. Ed., 47: 3747–3750. doi: 10.1002/anie.200705795
RabGGTase: Rab geranylgeranyl transferase. We thank the X-ray communities of the Max-Planck-Institut für molekulare Physiologie (Dortmund, Germany) and the Max-Planck-Institut für medizinische Forschung (Heidelberg, Germany) for collecting diffraction data at the Swiss Light Source of the Paul Scherrer Institute (Villigen, Switzerland) and for giving us generous access and support for the station X10SA. K.A. was supported by a Heisenberg Award of the Deutsche Forschungsgemeinschaft (DFG). This work was supported in part by DFG grants to K.A. (grant no.: AL 484/7-2) and to K.A., R.S.G, and H.W. (grant no.: SFB642), and by the Zentrum für Angewandte Chemische Genomik. R.S.B. thanks the Alexander von Humboldt Stiftung for a scholarship.
- Issue published online: 28 APR 2008
- Article first published online: 10 APR 2008
- Manuscript Received: 18 DEC 2007
- DFG. Grant Number: AL 484/7-2
- protein modifications;
- protein structures;
Stopping the transfer: Based on the structure of pepticinnamin E, specific inhibitors of Rab geranylgeranyl transferase (RabGGTase) with activity in cells were developed, and the first crystal structure of the enzyme in complex with an inhibitor is reported (see inhibitor structure and positioning in the active site of the enzyme). The findings may have implications for the chemical-biological study of Rab prenylation and vesicular transport and the involvement of RabGGTase in the establishment of disease.