3te4 | pdb_00003te4
Crystal structure of dopamine N Acetyltransferase in complex with acetyl-COA from Drosophila Melanogaster
Structural highlights
Function[DNAT_DROME] Catalyzes N-acetylation of tryptamine, tyramine, dopamine, serotonin and octopamine. Is not essential for sclerotization.[1] [2] [3] Publication Abstract from PubMedThe daily cycle of melatonin biosynthesis in mammals is regulated by arylalkylamine N-acetyltransferase (EC 2.3.1.87, AANAT), making it an attractive target for therapeutic control of abnormal melatonin production in mood and sleep disorders. Drosophila melanogaster dopamine N-acetyltransferase (Dat) is an AANAT. Until this report, no insect Dat structure had been solved, and consequently, the structural basis for its acetyl-transfer activity was not well understood. We report herein the high-resolution crystal structure for a D. melanogaster Dat/acetyl coenzyme A (AcCoA) complex obtained using one-edge (Selenium) single-wavelength anomalous diffraction. The binding study by isothermal titration calorimetry suggested that the cofactor bound to Dat first before substrate. Examination of the complex structure and a substrate-docked model indicated that Dat contains a novel AANAT catalytic triad. A site-directed mutagenesis, a kinetic study and pH-rate profiles confirmed that Glu47, Ser182, and Ser186 were critical for catalysis. Collectively, our results suggest that Dat possesses a specialized active site structure dedicated to a catalytic mechanism. Crystal Structure of Dopamine N-Acetyltransferase/Acetyl Coenzyme A Complex Provide Insights into the Catalytic Mechanism.,Cheng KC, Liao JN, Lyu PC Biochem J. 2012 Jun 21. PMID:22716280[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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