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From Proteopedia
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Serotonin N-acetyltransferase is also named aralkylamine-N-acetyltransferase (ANAAT). AANAT is a member of a large superfamily of proteins, referred to alternatively as the motif A/B or the GCN-5-related N-acetyltransferase (or GNAT) family. The role of these enzymes is to catalyse the acetylation all sorts of residues. | Serotonin N-acetyltransferase is also named aralkylamine-N-acetyltransferase (ANAAT). AANAT is a member of a large superfamily of proteins, referred to alternatively as the motif A/B or the GCN-5-related N-acetyltransferase (or GNAT) family. The role of these enzymes is to catalyse the acetylation all sorts of residues. | ||
| - | ANAAT catalyzes the acetylation of the amine group on serotonin, an intermediate in melatonin synthesis. It is the penultimate enzyme in the melatonin pathway, as it is shown on fig1.<ref>[1]</ref>. | + | ANAAT catalyzes the acetylation of the amine group on serotonin, an intermediate in melatonin synthesis. It is the penultimate enzyme in the melatonin pathway, as it is shown on fig1. <ref>[1]</ref>. |
[[Image:melationin synthesis.jpg]] | [[Image:melationin synthesis.jpg]] | ||
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Circulating melatonin plays a role in the circadian rythm. Day/night differences in circulating melatonin levels provide a hormonal analog signal of environmental lighting, which is used in a variety of ways to optimize circadian and circannual rhythms in physiology<ref>[2]. | Circulating melatonin plays a role in the circadian rythm. Day/night differences in circulating melatonin levels provide a hormonal analog signal of environmental lighting, which is used in a variety of ways to optimize circadian and circannual rhythms in physiology<ref>[2]. | ||
| - | The amount of circulating melatonin is correlated with ANAAT activity, as enzyme activity varies in parallel with melatonin amount. For example, in some species the night/day differences in melatonin, AANAT activity, and protein are 10- to 100-fold <ref>[3]<ref>[4]. | + | The amount of circulating melatonin is correlated with ANAAT activity, as enzyme activity varies in parallel with melatonin amount. For example, in some species the night/day differences in melatonin, AANAT activity, and protein are 10- to 100-fold <ref>[3]</ref><ref>[4]</ref>. |
| - | Defects in ANAAT regulation could be responsible for sleep troubles, such as insomnia or narcolepsy.<ref>[5] | + | Defects in ANAAT regulation could be responsible for sleep troubles, such as insomnia or narcolepsy.<ref>[5]</ref> |
== Structure == | == Structure == | ||
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<references /> | <references /> | ||
| - | == References == | ||
[1] Hickman, A. B; Klein, D. C; Dyda, F. Melatonin Biosynthesis: The Structure of Serotonin N-Acetyltransferase at 2.5A Resolution Suggests a Catalytic Mechanism. Mol. Cell. 1999, 3-1, 23-32. | [1] Hickman, A. B; Klein, D. C; Dyda, F. Melatonin Biosynthesis: The Structure of Serotonin N-Acetyltransferase at 2.5A Resolution Suggests a Catalytic Mechanism. Mol. Cell. 1999, 3-1, 23-32. | ||
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Contents |
Function
Serotonin N-acetyltransferase is also named aralkylamine-N-acetyltransferase (ANAAT). AANAT is a member of a large superfamily of proteins, referred to alternatively as the motif A/B or the GCN-5-related N-acetyltransferase (or GNAT) family. The role of these enzymes is to catalyse the acetylation all sorts of residues. ANAAT catalyzes the acetylation of the amine group on serotonin, an intermediate in melatonin synthesis. It is the penultimate enzyme in the melatonin pathway, as it is shown on fig1. [3].
Relevance
Circulating melatonin plays a role in the circadian rythm. Day/night differences in circulating melatonin levels provide a hormonal analog signal of environmental lighting, which is used in a variety of ways to optimize circadian and circannual rhythms in physiology[4][5]. Defects in ANAAT regulation could be responsible for sleep troubles, such as insomnia or narcolepsy.[6]
Structure
AANAT is a globular protein consisting of an 8-stranded β sheet with five α helices, with a conserved motif in the center of the sheet forming a binding site for acetyl-CoA, the acetyl source. Indeed, the active site is deeply burried into the protein, which is rare in the GNAT family. The access to this site is warranted for serotonin by and hydrophobic funnel formed by three polypeptide loops which converge above the acCoA binding site. (INSERT GREEN LINK HERE WHICH SHOWS THE HYDROPHOBIC FUINNEL AND THE ACTIVE SITE) At the bottom of the funnel, in the active site, are located two conserved histidines (GREEN LINK HERE) which suggest a catalytic mechanism for acetylation involving imidazole groups acting as a general acid/base catalysts. .[7]
Regulation
</StructureSection>
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
- ↑ [1]
- ↑ [2]. The amount of circulating melatonin is correlated with ANAAT activity, as enzyme activity varies in parallel with melatonin amount. For example, in some species the night/day differences in melatonin, AANAT activity, and protein are 10- to 100-fold <ref>[3]</li> <li id="cite_note-4">[[#cite_ref-4|↑]] [4]</li> <li id="cite_note-5">[[#cite_ref-5|↑]] [5]</li> <li id="cite_note-6">[[#cite_ref-6|↑]] [1]</li></ol></ref>
[1] Hickman, A. B; Klein, D. C; Dyda, F. Melatonin Biosynthesis: The Structure of Serotonin N-Acetyltransferase at 2.5A Resolution Suggests a Catalytic Mechanism. Mol. Cell. 1999, 3-1, 23-32.
[2] Arendt, J. (1995) Melatonin and the Mammalian Pineal Gland (Chapman & Hall, London), pp. 201–285.
[3] Klein, D.C., and Weller, J.L. (1972). Rapid light induced decrease in pineal serotonin N-acetyltransferase activity. Science 177, 532–533.
[4]Gastel, J.A., Roseboom, P.H., Rinaldi, P.A., Weller, J.L., and Klein,D.C. (1998). Melatonin production: proteasomal proteolysis in serotonin N-acetyltransferase regulation. Science 279, 1358–1360.
[5] Rati Srinivasan, Guy Gechtman, Abe Bayer. What is the Molecular Basis of Sleep Regulation, https://sites.tufts.edu/sleep/
[6] Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N -acetyltransferase mediated by phosphoserine-205 - Surajit Ganguly, Joan L. Weller, Anthony Ho, Philippe Chemineau, Benoit Malpaux, and David C. Klein - PNAS, January 25, 2005.
[7] The Structural Basis of Ordered Substrate Binding by Serotonin N-Acetyltransferase: Enzyme Complex at 1.8 A ˚ Resolution with a Bisubstrate Analog - Alison Burgess Hickman,M. A. A. Namboodiri, David C. Klein, and Fred Dyda - Cell, Vol. 97, 361–369, April 30, 1999.
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