title: eNOS activation and NO function: structural motifs responsible for the posttranslational control of endothelial nitric oxide synthase activity.
abstract: Rather than being a constitutive enzyme as was first suggested, endothelial nitric oxide synthase (eNOS) is dynamically regulated at the transcriptional, posttranscriptional, and posttranslational levels. This review will focus on how changes in eNOS function are conferred by various posttranslational modifications. The latest knowledge regarding eNOS targeting to the plasma membrane will be discussed as the role of protein phosphorylation as a modulator of catalytic activity. Furthermore, new data are presented that provide novel insights into how disruption of the eNOS dimer prevents eNOS uncoupling and the production of superoxide under conditions of elevated oxidative stress and identifies a novel regulatory region we have termed the 'flexible arm'.
authors.affiliation: Pulmonary Vascular Disease Program, Vascular Biology Center: CB-3211B, Georgia Health Sciences University, 1459 Laney Walker Boulevard, Augusta, GA 30912, USA.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Rafikov
authors.forename: Fabio V
authors.initials: FV
authors.lastname: Fonseca
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Kumar
authors.forename: Daniel
authors.initials: D
authors.lastname: Pardo
authors.forename: Charles
authors.initials: C
authors.lastname: Darragh
authors.forename: Shawn
authors.initials: S
authors.lastname: Elms
authors.forename: David
authors.initials: D
authors.lastname: Fulton
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Black
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D019281:Dimerization; D004789:Enzyme Activation; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D001708:Biopterins; D013912:Threonine; D009569:Nitric Oxide; D014443:Tyrosine; D012694:Serine; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin