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Electrostatic steering enhances the rate of cAMP binding to phosphodiesterase: Brownian dynamics modeling
Author(s) -
Huang Yuming M.,
Huber Gary,
Andrew McCammon J.
Publication year - 2015
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2794
Subject(s) - phosphodiesterase , second messenger system , biophysics , cyclic adenosine monophosphate , compartmentalization (fire protection) , intracellular , brownian dynamics , molecule , adenosine , chemistry , brownian motion , enzyme , microbiology and biotechnology , biology , physics , biochemistry , receptor , organic chemistry , quantum mechanics
Signaling in cells often involves co‐localization of the signaling molecules. Most experimental evidence has shown that intracellular compartmentalization restricts the range of action of the second messenger, 3'‐5'‐cyclic adenosine monophosphate (cAMP), which is degraded by phosphodiesterases (PDEs). The objective of this study is to understand the details of molecular encounter that may play a role in efficient operation of the cAMP signaling apparatus. The results from electrostatic potential calculations and Brownian dynamics simulations suggest that positive potential of the active site from PDE enhances capture of diffusing cAMP molecules. This electrostatic steering between cAMP and the active site of a PDE plays a major role in the enzyme‐substrate encounter, an effect that may be of significance in sequestering cAMP released from a nearby binding site or in attracting more freely diffusing cAMP molecules.