Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT
Zur Ablage hinzufügen
  Lokale TagsFreigabegeschichteDetailsÜbersicht

Freigegeben
Zeitschriftenartikel

Structural characterization of human tryptophan hydroxylase 2 reveals that L-Phe is superior to L-Trp as the regulatory domain ligand

MPG-Autoren
/persons/resource/persons251180

Zhang,  Zhenwei
Department of Structural Dynamics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons15857

Stark,  Holger
Department of Structural Dynamics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

Externe Ressourcen
Es sind keine externen Ressourcen hinterlegt
Volltexte (beschränkter Zugriff)
Für Ihren IP-Bereich sind aktuell keine Volltexte freigegeben.
Volltexte (frei zugänglich)
Es sind keine frei zugänglichen Volltexte in PuRe verfügbar
Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Vedel, I. M., Prestel, A., Zhang, Z., Skawinska, N. T., Stark, H., Harris, P., et al. (2023). Structural characterization of human tryptophan hydroxylase 2 reveals that L-Phe is superior to L-Trp as the regulatory domain ligand. Structure, 31(6), 689-699.e6. doi:10.1016/j.str.2023.04.004.


Zitierlink: https://hdl.handle.net/21.11116/0000-000D-B06C-3
Zusammenfassung
Tryptophan hydroxylase 2 (TPH2) catalyzes the rate-limiting step in serotonin biosynthesis in the brain. Consequently, regulation of TPH2 is relevant for serotonin-related diseases, yet the regulatory mechanism of TPH2 is poorly understood and structural and dynamical insights are missing. We use NMR spectroscopy to determine the structure of a 47 N-terminally truncated variant of the regulatory domain (RD) dimer of human TPH2 in complex with L-Phe, and show that L-Phe is the superior RD ligand compared with the natural substrate, L-Trp. Using cryo-EM, we obtain a low-resolution structure of a similarly truncated variant of the complete tetrameric enzyme with dimerized RDs. The cryo-EM two-dimensional (2D) class averages additionally indicate that the RDs are dynamic in the tetramer and likely exist in a monomer-dimer equilibrium. Our results provide structural information on the RD as an isolated domain and in the TPH2 tetramer, which will facilitate future elucidation of TPH2’s regulatory mechanism.