Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. A role for scaffolding in enzyme regulation

0142440 - FGU-C 20030041 RIV US eng J - Článek v odborném periodiku
Obšil, Tomáš - Ghirlando, R. - Klein, D. C. - Ganguly, S. - Dyda, F.
Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. A role for scaffolding in enzyme regulation.
Cell. Roč. 105, č. 2 (2001), s. 257-267. ISSN 0092-8674. E-ISSN 1097-4172
Výzkumný záměr: CEZ:AV0Z5011922
Klíčová slova: 14-3-3 * AANAT * crystal structure
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 29.210, rok: 2001

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.
Trvalý link: http://hdl.handle.net/11104/0040143