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

doi:10.1038/nsb1005

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

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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 language	English (US)
Pages (from-to)	1054-1057
Number of pages	4
Journal	Nature Structural Biology
Volume	10
Issue number	12
DOIs	https://doi.org/10.1038/nsb1005
State	Published - Dec 2003
Externally published	Yes

ASJC Scopus subject areas

Structural Biology
Biochemistry
Genetics

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title = "Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation",

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.",

author = "Weiping Zheng and Zhongsen Zhang and Surajit Ganguly and Weller, {Joan L.} and Klein, {David C.} and Cole, {Philip A.}",

note = "Funding Information: We thank D.B. Murphy and C.J. Janetopoulos for advice on microinjection and immunofluorescence experiments. We are grateful for financial support from the US National Institutes of Health and the Ellison Medical Foundation. Mass spectrometry analysis was carried out in the AB Mass Spectrometry/Proteomics Facility at Johns Hopkins School of Medicine with support from a US National Center for Research Resources shared instrumentation grant, the Johns Hopkins Fund for Medical Discovery and the Institute for Cell Engineering.",

year = "2003",

month = dec,

doi = "10.1038/nsb1005",

language = "English (US)",

volume = "10",

pages = "1054--1057",

journal = "Nature Structural Biology",

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T1 - Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation

AU - Zheng, Weiping

AU - Zhang, Zhongsen

AU - Ganguly, Surajit

AU - Weller, Joan L.

AU - Klein, David C.

AU - Cole, Philip A.

N1 - Funding Information: We thank D.B. Murphy and C.J. Janetopoulos for advice on microinjection and immunofluorescence experiments. We are grateful for financial support from the US National Institutes of Health and the Ellison Medical Foundation. Mass spectrometry analysis was carried out in the AB Mass Spectrometry/Proteomics Facility at Johns Hopkins School of Medicine with support from a US National Center for Research Resources shared instrumentation grant, the Johns Hopkins Fund for Medical Discovery and the Institute for Cell Engineering.

PY - 2003/12

Y1 - 2003/12

N2 - 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.

AB - 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.

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

Abstract

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