TY - JOUR
T1 - Principles of allosteric interactions in cell signaling
AU - Nussinov, Ruth
AU - Tsai, Chung Jung
AU - Liu, Jin
N1 - Publisher Copyright:
© 2014 American Chemical Society.
PY - 2014/12/24
Y1 - 2014/12/24
N2 - Linking cell signaling events to the fundamental physicochemical basis of the conformational behavior of single molecules and ultimately to cellular function is a key challenge facing the life sciences. Here we outline the emerging principles of allosteric interactions in cell signaling, with emphasis on the following points. (1) Allosteric efficacy is not a function of the chemical composition of the allosteric pocket but reflects the extent of the population shift between the inactive and active states. That is, the allosteric effect is determined by the extent of preferred binding, not by the overall binding affinity. (2) Coupling between the allosteric and active sites does not decide the allosteric effect; however, it does define the propagation pathways, the allosteric binding sites, and key on-path residues. (3) Atoms of allosteric effectors can act as "driver" or "anchor" and create attractive "pulling" or repulsive "pushing" interactions. Deciphering, quantifying, and integrating the multiple co-occurring events present daunting challenges to our scientific community.
AB - Linking cell signaling events to the fundamental physicochemical basis of the conformational behavior of single molecules and ultimately to cellular function is a key challenge facing the life sciences. Here we outline the emerging principles of allosteric interactions in cell signaling, with emphasis on the following points. (1) Allosteric efficacy is not a function of the chemical composition of the allosteric pocket but reflects the extent of the population shift between the inactive and active states. That is, the allosteric effect is determined by the extent of preferred binding, not by the overall binding affinity. (2) Coupling between the allosteric and active sites does not decide the allosteric effect; however, it does define the propagation pathways, the allosteric binding sites, and key on-path residues. (3) Atoms of allosteric effectors can act as "driver" or "anchor" and create attractive "pulling" or repulsive "pushing" interactions. Deciphering, quantifying, and integrating the multiple co-occurring events present daunting challenges to our scientific community.
UR - http://www.scopus.com/inward/record.url?scp=84919933634&partnerID=8YFLogxK
U2 - 10.1021/ja510028c
DO - 10.1021/ja510028c
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AN - SCOPUS:84919933634
SN - 0002-7863
VL - 136
SP - 17692
EP - 17701
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 51
ER -