1kuv

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spinqualitylabelsall models 1kuv, resolution 2.0Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

X-ray Crystallographic Studies of Serotonin N-acetyltransferase Catalysis and Inhibition

Overview

The structure of serotonin N-acetyltransferase (also known as, arylalkylamine N-acetyltransferase; AANAT) bound to a potent bisubstrate, analog inhibitor has been determined at 2.0 A resolution using a two-edge, (Se, Br) multiwavelength anomalous diffraction (MAD) experiment. This, acetyl-CoA dependent enzyme is a member of the GCN5-related family of, N-acetyltransferases (GNATs), which share four conserved sequence motifs, (A-D). In serotonin N-acetyltransferase, motif A adopts an alpha/beta, conformation characteristic of the phylogenetically invariant cofactor, binding site seen in all previously characterized GNATs. Motif B displays, a significantly lower level of conservation among family members, giving, rise to a novel alpha/beta structure for the serotonin binding slot., Utilization of a brominated CoA-S-acetyl-tryptamine-bisubstrate analog, inhibitor and the MAD method permitted conclusive identification of two, radically different conformations for the tryptamine moiety in the, catalytic site (cis and trans). A second high-resolution X-ray structure, of the enzyme bound to a bisubstrate analog inhibitor, with a longer, tether between the acetyl-CoA and tryptamine moieties, demonstrates only, the trans conformation. Given a previous proposal that AANAT can catalyze, an alkyltransferase reaction in a conformationally altered active site, relative to its acetyltransferase activity, it is possible that the two, conformations of the bisubstrate analog observed crystallographically, correspond to these alternative reaction pathways. Our findings may, ultimately lead to the design of analogs with improved AANAT inhibitory, properties for in vivo applications.

About this Structure

1KUV is a Single protein structure of sequence from Ovis aries with MG and CA5 as ligands. Active as Aralkylamine N-acetyltransferase, with EC number 2.3.1.87 Full crystallographic information is available from OCA.

Reference

X-ray crystallographic studies of serotonin N-acetyltransferase catalysis and inhibition., Wolf E, De Angelis J, Khalil EM, Cole PA, Burley SK, J Mol Biol. 2002 Mar 22;317(2):215-24. PMID:11902838

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