A point for discussion of the bc1 complex, a proton-pumping oxidoreductase of repiratory and photosynthetic electron transport chains.
Saturday, December 2, 2006
8> L. Esser, X. Gong, S. Yang, L. Yu, C.A. Yu and D. Xia, Surface-modulated motion switch: capture and release of iron-sulfur protein in the cytochrome bc1 complex, Proc Natl Acad Sci U S A 103 (2006) 13045-50.
1 comment:
Anonymous
said...
One criticism- this paper assumes the conformational changes in cyt b in the different structures are all caused by inhibitor binding, and they cause fixation of the ISP. Movement of the cd1 cd2 helix would seem more likely caused by docking of the ISP. Also remember Ulrich Brandt and coworkers showed that stigmatellin binds weakly and in a different way in the absence of the ISP. Until we get structures where the ISP-ED is absent or restrained by crystal contacts from docking, it will be impossible to trace causality: inhibitor -> docking -> conf change or inhibitor -> conf change -> docking
But it doesn't really matter- the surface-modulated switch hypothesis can be generalized to say that inhibitor binding causes/requires certain conformational changes, and ISP fixation causes/requires certain conformational changes. To the extent these conf changes are mutually exclusive, docking and inhibitor binding will be mutually exclusive, and to the extent they are similar docking and inhib binding will be cooperative. Now say that certain states of the reaction cycle result in or require conformational changes similar to the inhibitors which are mutually exclusive if ISP docking, and the bifurcation will be ensured. Ed Berry
1 comment:
One criticism- this paper assumes the conformational changes in cyt b in the different structures are all caused by inhibitor binding, and they cause fixation of the ISP. Movement of the cd1 cd2 helix would seem more likely caused by docking of the ISP.
Also remember Ulrich Brandt and coworkers showed that stigmatellin binds weakly and in a different way in the absence of the ISP.
Until we get structures where the ISP-ED is absent or restrained by crystal contacts from docking, it will be impossible to trace causality:
inhibitor -> docking -> conf change
or
inhibitor -> conf change -> docking
But it doesn't really matter- the surface-modulated switch hypothesis can be generalized to say that inhibitor binding causes/requires certain conformational changes, and ISP fixation causes/requires certain conformational changes. To the extent these conf changes are mutually exclusive, docking and inhibitor binding will be mutually exclusive, and to the extent they are similar docking and inhib binding will be cooperative. Now say that certain states of the reaction cycle result in or require conformational changes similar to the inhibitors which are mutually exclusive if ISP docking, and the bifurcation will be ensured.
Ed Berry
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