Sandbox Reserved 1506
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.[1]. | + | 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[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 [3][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>[4]. |
| - | Defects in ANAAT regulation could be responsible for sleep troubles, such as insomnia or narcolepsy.[5] | + | Defects in ANAAT regulation could be responsible for sleep troubles, such as insomnia or narcolepsy.<ref>[5] |
== Structure == | == 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. | + | 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) | 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. [1] | + | 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. .<ref>[1]</ref> |
[[Image:ANAAT-mechanism his catalysis.jpg]] | [[Image:ANAAT-mechanism his catalysis.jpg]] | ||
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</StructureSection> | </StructureSection> | ||
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| + | <references> | ||
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== References == | == References == | ||
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| - | < | + | </references> |
Revision as of 14:00, 2 January 2019
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| This Sandbox is Reserved from 06/12/2018, through 30/06/2019 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1480 through Sandbox Reserved 1543. |
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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]
Regulation
</StructureSection>
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