Protein Allostery and Conformational Dynamics #MMPMID26876046
Guo J; Zhou HX
Chem Rev 2016[Jun]; 116 (11): 6503-15 PMID26876046show ga
The functions of many proteins are regulated through allostery, whereby effector binding at a distal site changes the functional activity (e.g., substrate binding affinity or catalytic efficiency) at the active site. Most allosteric studies have focused on thermodynamic properties, in particular, substrate binding affinity. Changes in substrate binding affinity by allosteric effectors have generally been thought to be mediated by conformational transitions of the proteins, or alternatively, by changes in the broadness of the free energy basin of the protein conformational state without shifting the basin minimum position. When effector binding changes the free energy landscape of a protein in conformational space, the change not only affects thermodynamic properties but also dynamic properties, including the amplitudes of motions on different timescales and rates of conformational transitions. Here we assess the roles of conformational dynamics in allosteric regulation. Two cases are highlighted where NMR spectroscopy and molecular dynamics simulation have been used as complementary approaches to identify residues possibly involved in allosteric communication. Perspectives on contentious issues, e.g., the relation between picosecond-nanosecond local and microsecond-millisecond conformational exchange dynamics, are presented.
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Chem+Rev 2016 ; 116 (11): 6503-15
