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1FFW association rate - slow or fast ?

Posted by gautambasu on 05 Apr 2014 at 19:19 GMT

The PDB structure 1FFW is between CheY and residues 124 to 257 of CheA, encompassing the P2 domain.
The association rate between CheY and P2 domain of CheA is quite fast (log_kon ~ 8), as reported
by Stewart and Bruggen (J. Mol. Biol. 2004, 336:287-301). However, in the paper the rate constant for 1FFW
is quoted (referred from Schuster et. al. 1997, Nature 365: 343–347) as log_kon ~ 2.5.

No competing interests declared.

RE: 1FFW association rate - slow or fast ?

IMoal replied to gautambasu on 07 Apr 2014 at 10:33 GMT

Dear Gautam,
We used the association rate constant reported for the whole CheA interaction from the Schuster et al. article, and not for the P2 domain in isolation. We took the rate constants from the structural affinity benchmark (Kastristis et al. Protein Sci, 2011 20(3): 482-491), which does not include the Stewart and Bruggen value. The latter does better represent the crystal structure, and the derived affinity is in closer agreement with an independent measurement, also specifically for the P2 domain (Kd ~1.2e-6, D. Shukla and P. Matsumura, J Biol Chem, 1995, 270(41):24414-9). This appears to support that the kinetics are fast and not slow as assumed in our article. It does seem remarkable, however, that the additional domains would simultaneously slow the rate of association by five orders of magnitude and slow the rate of dissociation by six orders of magnitude. Nevertheless, thank you for bringing this to our attention, and we will make sure to correct the future affinity benchmark to reflect this.

Regards,
Iain H. Moal and Paul A. Bates

No competing interests declared.