Calmodulin Activates Neuronal Nitric Oxide Synthase by Enabling Transitions between Conformational States

Authors

John C. Salerno, Kennesaw State UniversityFollow
Krishanu Ray, University of Maryland - Baltimore
Thomas Poulos, University of California - Irvine
Huiying Li, University of California - Irvine
Dipak K. Ghosh, Duke University

Department

Molecular and Cellular Biology

Document Type

Article

Publication Date

1-4-2013

Abstract

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.