 |
PDBsum entry 1b6b
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Melatonin biosynthesis: the structure of serotonin n-Acetyltransferase at 2.5 a resolution suggests a catalytic mechanism.
|
|
|
Authors
|
|
A.B.Hickman,
D.C.Klein,
F.Dyda.
|
|
|
Ref.
|
|
Mol Cell, 1999,
3,
23-32.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Conversion of serotonin to N-acetylserotonin, the precursor of the circadian
neurohormone melatonin, is catalyzed by serotonin N-acetyltransferase (AANAT) in
a reaction requiring acetyl coenzyme A (AcCoA). AANAT is a globular protein
consisting of an eight-stranded beta sheet flanked by five alpha helices; a
conserved motif in the center of the beta sheet forms the cofactor binding site.
Three polypeptide loops converge above the AcCoA binding site, creating a
hydrophobic funnel leading toward the cofactor and serotonin binding sites in
the protein interior. Two conserved histidines not found in other NATs are
located at the bottom of the funnel in the active site, suggesting a catalytic
mechanism for acetylation involving imidazole groups acting as general acid/base
catalysts.
|
|
|
|
|
|
|
|
Figure 5.
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.
|
|
Figure 6.
Figure 6. Proposed Catalytic MechanismThe 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.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(1999,
3,
23-32)
copyright 1999.
|
|
|
|
|
|
|
