Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation

Weiping Zheng, Zhongsen Zhang, Surajit Ganguly, Joan L. Weller, David C. Klein, Philip A. Cole

Research output: Contribution to journalArticle

Abstract

Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) controls daily changes in the production and circulating levels of melatonin. Here, the significance of the phosphorylation of AANAT was studied using a semisynthetic enzyme in which a nonhydrolyzable phosphoserine/threonine mimetic, phosphonomethylenealanine (Pma), was incorporated at position 31 (AANAT-Pma31). The results of studies in which AANAT-Pma31 and related analogs were injected into cells provide the first direct evidence that Thr31 phosphorylation controls AANAT stability in the context of the intact cells by binding to 14-3-3 protein. These findings establish Thr31 phosphorylation as an essential element in the intracellular regulation of melatonin production. The application of Pma in protein semisynthesis is likely to be broadly useful in the analysis of protein serine/threonine phosphorylation.

Original languageEnglish (US)
Pages (from-to)1054-1057
Number of pages4
JournalNature Structural Biology
Volume10
Issue number12
DOIs
StatePublished - Dec 2003

Fingerprint

Arylalkylamine N-Acetyltransferase
Organophosphonates
Melatonin
Phosphorylation
Stabilization
Enzymes
Threonine
14-3-3 Proteins
Phosphoserine
Serine
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Zheng, W., Zhang, Z., Ganguly, S., Weller, J. L., Klein, D. C., & Cole, P. A. (2003). Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation. Nature Structural Biology, 10(12), 1054-1057. https://doi.org/10.1038/nsb1005

Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation. / Zheng, Weiping; Zhang, Zhongsen; Ganguly, Surajit; Weller, Joan L.; Klein, David C.; Cole, Philip A.

In: Nature Structural Biology, Vol. 10, No. 12, 12.2003, p. 1054-1057.

Research output: Contribution to journalArticle

Zheng, W, Zhang, Z, Ganguly, S, Weller, JL, Klein, DC & Cole, PA 2003, 'Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation', Nature Structural Biology, vol. 10, no. 12, pp. 1054-1057. https://doi.org/10.1038/nsb1005
Zheng, Weiping ; Zhang, Zhongsen ; Ganguly, Surajit ; Weller, Joan L. ; Klein, David C. ; Cole, Philip A. / Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation. In: Nature Structural Biology. 2003 ; Vol. 10, No. 12. pp. 1054-1057.
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