Insights into the interaction of high potency inhibitor IRC-083864 with phosphatase CDC25.CDC25 phosphatases play a crucial role in cell cycle regulation.  Here, we report the first model of binding of the most potent CDC25 inhibitor to date, the bis-quinone IRC-083864, into CDC25B obtained by combining molecular modeling and NMR studies.  The docking model reveals that IRC-083864 occupies both the active site and the inhibitor binding pocket of the CDC25B catalytic domain.  Probing interactions of analogues of the two quinone units of IRC-083864 with CDC25B demonstrate that IRC-083864 competes with each monomer. 
IRC-083864
Insights into the interaction of high potency inhibitor IRC-083864 with phosphatase CDC25.CDC25 phosphatases play a crucial role in cell cycle regulation.  Here, we report the first model of binding of the most potent CDC25 inhibitor to date, the bis-quinone IRC-083864, into CDC25B obtained by combining molecular modeling and NMR studies.  Our study provides new insights into key interactions of the catalytic site inhibitor and CDC25B in the absence of any available experimental structure of CDC25 with a bound catalytic site inhibitor.  The docking model reveals that IRC-083864 occupies both the active site and the inhibitor binding pocket of the CDC25B catalytic domain.  Probing interactions of analogues of the two quinone units of IRC-083864 with CDC25B demonstrate that IRC-083864 competes with each monomer. 
CDC25
Here, we report the first model of binding of the most potent CDC25 inhibitor to date, the bis-quinone IRC-083864, into CDC25B obtained by combining molecular modeling and NMR studies.  NMR saturation transfer difference and WaterLOGSY data indicate the binding zones of the inhibitor and support the docking model. 
NMR
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