title: Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. a role for scaffolding in enzyme regulation.
abstract: Serotonin N-acetyltransferase (AANAT) controls the daily rhythm in melatonin synthesis. When isolated from tissue, AANAT copurifies with isoforms epsilon and zeta of 14-3-3. We have determined the structure of AANAT bound to 14-3-3zeta, an association that is phosphorylation dependent. AANAT is bound in the central channel of the 14-3-3zeta dimer, and is held in place by extensive interactions both with the amphipathic phosphopeptide binding groove of 14-3-3zeta and with other parts of the central channel. Thermodynamic and activity measurements, together with crystallographic analysis, indicate that binding of AANAT by 14-3-3zeta modulates AANAT's activity and affinity for its substrates by stabilizing a region of AANAT involved in substrate binding.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: T
authors.initials: T
authors.lastname: Obsil
authors.forename: R
authors.initials: R
authors.lastname: Ghirlando
authors.forename: D C
authors.initials: DC
authors.lastname: Klein
authors.forename: S
authors.initials: S
authors.lastname: Ganguly
authors.forename: F
authors.initials: F
authors.lastname: Dyda
mesh_terms: D048948:14-3-3 Proteins; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002151:Calorimetry; D018360:Crystallography, X-Ray; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012756:Sheep; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D011993:Recombinant Fusion Proteins; D014446:Tyrosine 3-Monooxygenase; D001191:Arylamine N-Acetyltransferase