title: Calmodulin activates neuronal nitric oxide synthase by enabling transitions between conformational states.
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.
authors.affiliation: Department of Biology, Kennesaw State University, Kennesaw, GA 30144, United States. jsalern3@kennesaw.edu
authors.forename: John C
authors.initials: JC
authors.lastname: Salerno
authors.forename: Krishanu
authors.initials: K
authors.lastname: Ray
authors.forename: Thomas
authors.initials: T
authors.lastname: Poulos
authors.forename: Huiying
authors.initials: H
authors.lastname: Li
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Ghosh
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D005486:Flavin Mononucleotide / Q000378:metabolism; D006427:Hemin / Q000378:metabolism; D020035:Holoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D002147:Calmodulin; D020035:Holoenzymes; D050505:Mutant Proteins; D011994:Recombinant Proteins; D006427:Hemin; D005486:Flavin Mononucleotide; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I