PDBsum entry 1b6b

Transferase

PDB id: 1b6b

Contents

Protein chains

168 a.a. *

156 a.a. *

Waters ×132

* Residue conservation analysis

PDB id:

1b6b

Name:

Transferase

Title:

Melatonin biosynthesis: the structure of serotonin n-acetyltransferase at 2.5 a resolution suggests a catalytic mechanism

Structure:

Protein (arylalkylamine n-acetyltransferase). Chain: a, b. Engineered: yes

Source:

Ovis aries. Sheep. Organism_taxid: 9940. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.50Å R-factor: 0.217 R-free: 0.282

Authors:

A.B.Hickman,D.C.Klein,F.Dyda

Key ref:

A.B.Hickman et al. (1999). Melatonin biosynthesis: the structure of serotonin N-acetyltransferase at 2.5 A resolution suggests a catalytic mechanism. Mol Cell, 3, 23-32. PubMed id: 10024876 DOI: 10.1016/S1097-2765(00)80171-9

Date:

13-Jan-99 Release date: 14-Jan-00

Protein chain

Q29495  (SNAT_SHEEP) -  Serotonin N-acetyltransferase from Ovis aries

Seq: 207 a.a.

Struc: 168 a.a.

Protein chain

Q29495  (SNAT_SHEEP) -  Serotonin N-acetyltransferase from Ovis aries

Seq: 207 a.a.

Struc: 156 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.2.3.1.87 - aralkylamine N-acetyltransferase.
• Reaction: a 2-arylethylamine + acetyl-CoA = an N-acetyl-2-arylethylamine + CoA + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/S1097-2765(00)80171-9

Mol Cell 3:23-32 (1999)

PubMed id: 10024876

Melatonin biosynthesis: the structure of serotonin N-acetyltransferase at 2.5 A resolution suggests a catalytic mechanism.

A.B.Hickman, D.C.Klein, F.Dyda.

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.

Selected figure(s)

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.

Figures were selected by an automated process.