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Cover Picture: Surface Change of Ras Enabling Effector Binding Monitored in Real Time at Atomic Resolution (ChemBioChem 7/2007)
Author(s) -
Kötting Carsten,
Kallenbach Angela,
Suveyzdis Yan,
Eichholz Carolin,
Gerwert Klaus
Publication year - 2007
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200790016
Subject(s) - gtp' , chemistry , protein data bank (rcsb pdb) , effector , molecular switch , flash photolysis , gtpase , biophysics , molecule , analytical chemistry (journal) , crystallography , reaction rate constant , stereochemistry , biochemistry , biology , kinetics , enzyme , organic chemistry , physics , quantum mechanics
The cover picture shows the switch‐I movement that turns the Ras protein from the off‐signalling to the on‐signalling state (Ras off GTP (PDB ID: 1X1S) to Ras on GTP (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 (Ras off GTP). A small molecule that is able to shift the equilibrium from Ras on GTP to Ras off GTP 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.