1kuv | pdb_00001kuv

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

spinqualitylabelsall models 1kuv, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1kuv is a 1 chain structure with sequence from Ovis aries. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: CA5, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SNAT_SHEEP Controls the night/day rhythm of melatonin production in the pineal gland. Catalyzes the N-acetylation of serotonin into N-acetylserotonin, the penultimate step in the synthesis of melatonin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serotonin N-acetyltransferase

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