ChemBioChem

Cover image for Vol. 18 Issue 12

Editor: Meghan Campbell; Editorial Board Chairs: Thomas Carell, Donald Hilvert, Barbara Imperiali

Online ISSN: 1439-7633

Associated Title(s): ChemCatChem, ChemMedChem, ChemPhysChem, ChemSusChem

8_07/2007Cover Picture: Surface Change of Ras Enabling Effector Binding Monitored in Real Time at Atomic Resolution (ChemBioChem 7/2007)

The cover picture shows the switch-I movement that turns the Ras protein from the off-signalling to the on-signalling state (RasoffGTP (PDB ID: 1X1S) to RasonGTP (PDB ID: 5P21)). Time-resolved FTIR spectroscopy monitors the switch-I movement in real time with a rate constant of 5 s−1 at 260 K by using the carbonyl vibration of Thr35 as a marker. This absorption was assigned by means of isotopically labelled Ras. Laser flash photolysis of para-hydroxyphenacyl-caged GTP triggers the reaction within nanoseconds. Surprisingly, we identified a nonsignalling Ras state even when GTP is bound (RasoffGTP). A small molecule that is able to shift the equilibrium from RasonGTP to RasoffGTP in oncogenic mutations would prevent uncontrolled signalling. The IR difference spectrum can then be used as a spectroscopic fingerprint in a screening assay for such small molecules. For further information see the full paper by C. Kötting, K. Gewert, et al. on p. 781 ff.

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