3TE4
Crystal structure of dopamine N Acetyltransferase in complex with acetyl-COA from Drosophila Melanogaster
Summary for 3TE4
| Entry DOI | 10.2210/pdb3te4/pdb |
| Descriptor | Dopamine N acetyltransferase, isoform A, ACETYL COENZYME *A (3 entities in total) |
| Functional Keywords | transferase, dopamine/acetyl coa, n-acetyltransferase domain |
| Biological source | Drosophila melanogaster (Fruit fly) |
| Total number of polymer chains | 1 |
| Total formula weight | 25251.62 |
| Authors | Cheng, K.C.,Huang, S.H.,Lyu, P.C. (deposition date: 2011-08-12, release date: 2012-07-11, Last modification date: 2024-03-20) |
| Primary citation | Cheng, K.C.,Liao, J.N.,Lyu, P.C. Crystal structure of the dopamine N-acetyltransferase-acetyl-CoA complex provides insights into the catalytic mechanism Biochem.J., 446:395-404, 2012 Cited by PubMed Abstract: The daily cycle of melatonin biosynthesis in mammals is regulated by AANAT (arylalkylamine N-acetyltransferase; EC 2.3.1.87), making it an attractive target for therapeutic control of abnormal melatonin production in mood and sleep disorders. Drosophila melanogaster Dat (dopamine N-acetyltransferase) is an AANAT. Until the present study, no insect Dat structure had been solved, and, consequently, the structural basis for its acetyl-transfer activity was not well understood. We report in the present paper the high-resolution crystal structure for a D. melanogaster Dat-AcCoA (acetyl-CoA) complex obtained using one-edge (selenium) single-wavelength anomalous diffraction. A binding study using 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. Site-directed mutagenesis, kinetic studies and pH-rate profiles confirmed that Glu(47), Ser(182) and Ser(186) were critical for catalysis. Collectively, the results of the present study suggest that Dat possesses a specialized active site structure dedicated to a catalytic mechanism. PubMed: 22716280DOI: 10.1042/BJ20120520 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.46 Å) |
Structure validation
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