title: Mutations at lysine 525 of inducible nitric-oxide synthase affect its Ca2+-independent activity.
abstract: Calmodulin binding to inducible nitric-oxide synthase may play an important role in its Ca(2+)-independent activity. Studies of inducible nitric-oxide synthase chimeras containing the calmodulin binding sequence of neuronal or endothelial nitric-oxide synthases show that the calmodulin binding sequence of inducible nitric-oxide synthase is necessary but not sufficient for the Ca(2+)-independent activity. The mutations at lysine 525 located at the C terminus of the calmodulin binding sequence of inducible nitric-oxide synthase were examined for the effects on the Ca(2+)-independent activity with chimeras containing the oxygenase or reductase domains of inducible or neuronal nitric-oxide synthases. Results show that the Ca(2+)-independent binding of calmodulin is not solely responsible for maximal Ca(2+)-independent activity of inducible nitric-oxide synthase. Lysine 525 of inducible nitric-oxide synthase may also play an important role in coordinating the maximal Ca(2+)-independent activity.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9040, USA. slee@resgen.com
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
authors.forename: K
authors.initials: K
authors.lastname: Beckingham
authors.forename: J T
authors.initials: JT
authors.lastname: Stull
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014268:Trifluoperazine / Q000494:pharmacology
chemical_list: D002147:Calmodulin; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D014268:Trifluoperazine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D008239:Lysine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester