RT Journal Article
SR Electronic
T1 Relative contributions of conformational selection and induced fit
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 045591
DO 10.1101/045591
A1 Denis Michel
YR 2016
UL http://biorxiv.org/content/early/2016/03/24/045591.abstract
AB A long standing debate in biochemistry is to determine if the conformational changes observed during biomolecular interactions proceed through con-formational selection (of preexisting isoforms) or induced fit (ligand-induced 3D reshaping). The latter mechanism had been invoked in certain circumstances, for example to explain the non-Michalelian activity of monomeric enzymes like glucokinase. But the relative importance of induced fit has been recently depreciated in favor of con-formational selection, assumed to be always sufficient, predominant in general and in particular for glucokinase. This question is reconsidered here through different approaches, in and out of equilibrium, using single molecule state probability, one way fluxes and net fluxes. In equilibrium, the conditions for a switch from conformational selection to induced fit at a given ligand concentration are explicited. Out of equilibrium, the simple inspection of the enzyme states circuit shows that conformational selection alone can not explain the nonlinear behavior of glucokinase and would give a Michaelian reaction rate. Moreover, when induced fit and conformational selection coexist and allow kinetic cooperativity, the net flux emerging in the linkage cycle is necessarily oriented in the direction of the induced fit path.CSconformational selection;IFinduced fit