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| | ==Crystal structure of dopamine N Acetyltransferase in complex with acetyl-COA from Drosophila Melanogaster== | | ==Crystal structure of dopamine N Acetyltransferase in complex with acetyl-COA from Drosophila Melanogaster== |
| - | <StructureSection load='3te4' size='340' side='right' caption='[[3te4]], [[Resolution|resolution]] 1.46Å' scene=''> | + | <StructureSection load='3te4' size='340' side='right'caption='[[3te4]], [[Resolution|resolution]] 1.46Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3te4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TE4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TE4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3te4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TE4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CG3318, Dat, Dmel_CG3318 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CG3318, Dat, Dmel_CG3318 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3te4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3te4 OCA], [http://pdbe.org/3te4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3te4 RCSB], [http://www.ebi.ac.uk/pdbsum/3te4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3te4 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3te4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3te4 OCA], [https://pdbe.org/3te4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3te4 RCSB], [https://www.ebi.ac.uk/pdbsum/3te4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3te4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DNAT_DROME DNAT_DROME]] Catalyzes N-acetylation of tryptamine, tyramine, dopamine, serotonin and octopamine. Is not essential for sclerotization.<ref>PMID:8901578</ref> <ref>PMID:9703021</ref> <ref>PMID:7498465</ref> | + | [[https://www.uniprot.org/uniprot/DNAT_DROME DNAT_DROME]] Catalyzes N-acetylation of tryptamine, tyramine, dopamine, serotonin and octopamine. Is not essential for sclerotization.<ref>PMID:8901578</ref> <ref>PMID:9703021</ref> <ref>PMID:7498465</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Drome]] | | [[Category: Drome]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Cheng, K C]] | | [[Category: Cheng, K C]] |
| | [[Category: Huang, S H]] | | [[Category: Huang, S H]] |
| 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 PubMed
The 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
- ↑ Hintermann E, Grieder NC, Amherd R, Brodbeck D, Meyer UA. Cloning of an arylalkylamine N-acetyltransferase (aaNAT1) from Drosophila melanogaster expressed in the nervous system and the gut. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12315-20. PMID:8901578
- ↑ Brodbeck D, Amherd R, Callaerts P, Hintermann E, Meyer UA, Affolter M. Molecular and biochemical characterization of the aaNAT1 (Dat) locus in Drosophila melanogaster: differential expression of two gene products. DNA Cell Biol. 1998 Jul;17(7):621-33. PMID:9703021
- ↑ Hintermann E, Jeno P, Meyer UA. Isolation and characterization of an arylalkylamine N-acetyltransferase from Drosophila melanogaster. FEBS Lett. 1995 Nov 13;375(1-2):148-50. PMID:7498465
- ↑ Cheng KC, Liao JN, Lyu PC. Crystal Structure of Dopamine N-Acetyltransferase/Acetyl Coenzyme A Complex Provide Insights into the Catalytic Mechanism. Biochem J. 2012 Jun 21. PMID:22716280 doi:10.1042/BJ20120520
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