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| | ==Crystal structure of human N-acetylserotonin methyltransferase (ASMT) in complex with SAM and N-acetylserotonin== | | ==Crystal structure of human N-acetylserotonin methyltransferase (ASMT) in complex with SAM and N-acetylserotonin== |
| - | <StructureSection load='4a6e' size='340' side='right' caption='[[4a6e]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4a6e' size='340' side='right'caption='[[4a6e]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4a6e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A6E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A6E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4a6e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A6E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A6E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ASE:N-ACETYL+SEROTONIN'>ASE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4a6d|4a6d]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASE:N-ACETYL+SEROTONIN'>ASE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetylserotonin_O-methyltransferase Acetylserotonin O-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.4 2.1.1.4] </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=4a6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a6e OCA], [https://pdbe.org/4a6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a6e RCSB], [https://www.ebi.ac.uk/pdbsum/4a6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a6e ProSAT]</span></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=4a6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a6e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a6e RCSB], [http://www.ebi.ac.uk/pdbsum/4a6e PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ASMT_HUMAN ASMT_HUMAN]] Isoform 1 catalyzes the transfer of a methyl group onto N-acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine). Isoform 2 and isoform 3 lack enzyme activity.<ref>PMID:22775292</ref> | + | [https://www.uniprot.org/uniprot/ASMT_HUMAN ASMT_HUMAN] Isoform 1 catalyzes the transfer of a methyl group onto N-acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine). Isoform 2 and isoform 3 lack enzyme activity.<ref>PMID:22775292</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4a6e" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Acetylserotonin O-methyltransferase]] | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Haouz, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Legrand, P]] | + | [[Category: Haouz A]] |
| - | [[Category: Shepard, W]] | + | [[Category: Legrand P]] |
| - | [[Category: Circadian clock]] | + | [[Category: Shepard W]] |
| - | [[Category: Melatonin]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
4a6e is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.7Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
ASMT_HUMAN Isoform 1 catalyzes the transfer of a methyl group onto N-acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine). Isoform 2 and isoform 3 lack enzyme activity.[1]
Publication Abstract from PubMed
Melatonin is a synchronizer of many physiological processes. Abnormal melatonin signaling is associated with human disorders related to sleep, metabolism, and neurodevelopment. Here, we present the X-ray crystal structure of human N-acetyl serotonin methyltransferase (ASMT), the last enzyme of the melatonin biosynthesis pathway. The polypeptide chain of ASMT consists of a C-terminal domain, which is typical of other SAM-dependent O-methyltransferases, and an N-terminal domain, which intertwines several helices with another monomer to form the physiologically active dimer. Using radioenzymology, we analyzed 20 nonsynonymous variants identified through the 1000 genomes project and in patients with neuropsychiatric disorders. We found that the majority of these mutations reduced or abolished ASMT activity including one relatively frequent polymorphism in the Han Chinese population (N17K, rs17149149). Overall, we estimate that the allelic frequency of ASMT deleterious mutations ranges from 0.66% in Europe to 2.97% in Asia. Mapping of the variants on to the 3-dimensional structure clarifies why some are harmful and provides a structural basis for understanding melatonin deficiency in humans.
Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway.,Botros HG, Legrand P, Pagan C, Bondet V, Weber P, Ben-Abdallah M, Lemiere N, Huguet G, Bellalou J, Maronde E, Beguin P, Haouz A, Shepard W, Bourgeron T J Pineal Res. 2012 Jun 12. doi: 10.1111/j.1600-079X.2012.01020.x. PMID:22775292[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Botros HG, Legrand P, Pagan C, Bondet V, Weber P, Ben-Abdallah M, Lemiere N, Huguet G, Bellalou J, Maronde E, Beguin P, Haouz A, Shepard W, Bourgeron T. Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. J Pineal Res. 2012 Jun 12. doi: 10.1111/j.1600-079X.2012.01020.x. PMID:22775292 doi:10.1111/j.1600-079X.2012.01020.x
- ↑ Botros HG, Legrand P, Pagan C, Bondet V, Weber P, Ben-Abdallah M, Lemiere N, Huguet G, Bellalou J, Maronde E, Beguin P, Haouz A, Shepard W, Bourgeron T. Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. J Pineal Res. 2012 Jun 12. doi: 10.1111/j.1600-079X.2012.01020.x. PMID:22775292 doi:10.1111/j.1600-079X.2012.01020.x
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