Serotonin N-Acetyltransferase
Melatonin, a hormone that controls the day-night cycle, is synthesized by the following reaction. Serotonin N-Acetyltransferase (arylalkylamine-N-acetyltransferase or AANAT) catalyzes a transfer of an acetyl group (CH3-C=O) to serotonin. The product of this reaction, N-acetylserotonin, is further methylated (adding a methyl group, -CH3) by hydroxyindole-O-methyltransferase (HIOMT) to produce melatonin.
The focus of this tutorial is on the enzyme serotonin N-acetyltransferase. The 'Enzyme' button below will give a picture to the right of this enzyme in a ball and stick model. The coloring system is called CPK. This denotes carbon atoms as grey, oxygen atoms as red, nitrogen atoms as blue, sulfur atoms as yellow, and phosphorous atoms as orange. Though the general molecular outline is shown, it does not tell everything about this enzyme.
Enzyme with LigandThe picture to the right represents two uncomplexed (or those lacking the ligand CoA-S-Acetyltryptamine) serotonin N-acetyltransferase molecules. There is also a picture below. Structure A shows the uncomplexed enzyme, the orange portion represents the strand that undergoes a conformational change upon addition of the ligand CoA-S-Acetyltryptamine. Structure B shows the enzyme serotonin N-acetyltransferase bound and conformed to the ligand, where a new α helix is created.
As described, serotonin N-acetyltransferase transfers an acetyl group to serotonin to create N-acetylserotonin. The button below, 'Ligand', highlights the ligand CoA-S-acetyltryptamine in green. The enzyme transfers the acetyl group (remember: CH3-C=O) from the ligand to a molecule of serotonin (not pictured). After serotonin N-acetyltransferase takes the acetyl group from CoA-S-acetyltryptamine, the ligand leaves a binding space for serotonin to enter and take up the acetyl group. The first picture below features a schematic of the interactions of the ligand and the enzyme amino acids. The ligand CoA-S-acetyltryptamine is held in place largely by hydrogen bonding forces. The second picture, labeled 'B' shows the reaction mechanism of the acetyl group transfer.
Ligand
The active site of serotonin N-acetyltransferase is compromised of a 'V' that is created by the beta sheet in the interior of the enzyme. The loops are present over the 'V' create a funnel to the center of the molecule that is hydrophobic. This can be seen in the button below 'Hydrophobic Portions.' This shows the hydrophobic portions in white, hydrophilic in yellow, and the ligand in red. The beta sheets are represented by the long winding arrows, generally found in the center of the molecule, which will turn to show the 'V'.
Hydrophobic PortionsAll images and information adapted from Hickman et al. 'The Structural Basis of Ordered Substrate Binding by Serotonin N-Acetyltransferase: Enzyme Complex at 1.8 A Resolution with a Bisubstrate Analog', 1999.
All Jmol portions adapted from RCSB Protein Data Bank: rcsb.org. PDB ID's included were 1CJW and 1B6B.