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Calmodulin activates neuronal nitric oxide synthase by enabling transitions between conformational states
Author(s) -
Salerno John C.,
Ray Krishanu,
Poulos Thomas,
Li Huiying,
Ghosh Dipak K.
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.10.039
Subject(s) - calmodulin , nitric oxide synthase , chemistry , conformational change , atp synthase , nitric oxide , enzyme , biophysics , stereochemistry , biochemistry , biology , organic chemistry
We recently showed that inducible nitric oxide synthase conformational intermediates can be resolved via FMN fluorescence lifetimes. Here we show that neuronal NOS activation by calmodulin removes constraints favoring a closed ‘input state’, increasing occupation of other states and facilitating conformational transitions. The 90 ps FMN input state lifetime distinguishes it from ∼4 ns ‘open’ states in which FMN does not interact strongly with other groups, or 0.9 ns output states in which FMN interacts with ferriheme. Enablement of the conformational cycle is an important paradigm for control in nNOS and related enzymes, and may extend to other control modalities.