1. Melatonin Biosynthesis
Alison Burgess Hickman, David C. Klein, Fred Dyda 
Molecular Cell 
Volume 3, Issue 1, Pages (January 1999)
DOI: /S (00)

2. Figure 1
Synthesis of Melatonin from Serotonin and the Protein Fold of Serotonin N-Acetyltransferase
(A) Biochemical pathway for the synthesis of melatonin from serotonin. Serotonin (5-hydroxy-tryptamine) is converted to melatonin through the sequential action of two enzymes, serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, or AANAT) and hydroxyindole-O-methyltransferase (HIOMT). While levels of HIOMT activity remain fairly constant, the daily rhythm in melatonin synthesis is generated by a concurrent rhythm in AANAT activity.
(B) MOLSCRIPT (Kraulis 1991) stereo picture of the fold of AANAT28–201. There is a central eight-stranded β sheet flanked by five α helices; all the strands are antiparallel except for strands β5 and β6.
Molecular Cell 1999 3, 23-32DOI: ( /S (00) )

3. Figure 2 The β Sheets of AANAT
The central β sheet can be viewed as two β sheets sharing strands β4 and β5 with the strand order 1,3,4,5,2 and 4,5,6,8,7. In this orientation, the β bulge of Ala-123 immediately following the catalytically essential His-122 on strand β5 can be clearly seen. In structures where β bulges have been identified, they often appear at active sites or at positions where they accentuate the twist of the β sheet (Richardson 1981). The β bulge at Ala-123 appears to play both roles in AANAT.
Molecular Cell 1999 3, 23-32DOI: ( /S (00) )

4. Figure 3
Structure-Based Sequence Alignment of Primary Sequences of AANAT, Hat1, and AAT
β strands are shown in pink and helices in green. The boxes indicate the residues identified as motifs C, D, A, and B (Coon et al. 1995; Neuwald and Landsman 1997). Residues in italics indicate amino acids present in the protein constructs for which no corresponding electron density was found. The numbers above the sequence are for AANAT; the dots indicate every tenth residue.
Molecular Cell 1999 3, 23-32DOI: ( /S (00) )

5. Figure 4 Structure of Acetyl CoA and Modeled Binding to AANAT
(A) Structure of acetyl CoA. The two asteriskes mark the bond about which a severe kink is observed in the structures of Hat1 (Dutnall et al. 1998) and AAT (Wolf et al. 1998).
(B) Ribbons (Carson 1991) diagram showing the modeled binding of AcCoA and the positions of the conserved residues Cys-160, His-120, and His-122; His-122 is held in place by a hydrogen bond to Ser-97 and through van der Waals interactions with Phe-73. For clarity, the adenine and ribose groups of AcCoA are omitted since these are not uniquely positioned in the structures of Hat1 and AAT (Dutnall et al. 1998; Wolf et al. 1998). To model the binding of AcCoA, it was necessary to move the polypeptide chain in the region of strand β2 slightly since these residues were occupying part of the cofactor binding site (for comparison, see Figure 1B and Figure 5A). The three loops that form the funnel leading to the active site are numbered in blue.
Molecular Cell 1999 3, 23-32DOI: ( /S (00) )

6. Figure 5 The Serotonin Binding Site Is Buried in the Protein Interior
(A) Hydrophobic residues lining the funnel. For clarity, only the acetyl and β-mercaptoethyl groups of AcCoA are shown modeled in the active site.
(B) View into the hydrophobic funnel looking down toward ND1 of His-122 (in blue); the surrounding hydrophobic residues are shown in white. Figure was created by PovChem (P. Thiessen, Chem. Dept., School of Chemical Sciences, U. of Illinois at Urbana-Champaign), a front end for POV-Ray 3.0.
Molecular Cell 1999 3, 23-32DOI: ( /S (00) )

7. Figure 6 Proposed Catalytic Mechanism
The proposed mechanism involving His-122 as a general base catalyst in substrate deprotonation, and the subsequent formation of a tetravalent intermediate. The conserved residue Tyr-168 is positioned 3.5 Å away from the modeled position of the sulfur atom of AcCoA and could serve as a general acid catalyst to protonate the incipient thiolate anion of CoA. AAA stands for an arylalkylamine substrate.
Molecular Cell 1999 3, 23-32DOI: ( /S (00) )