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| | <StructureSection load='1l0c' size='340' side='right'caption='[[1l0c]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='1l0c' size='340' side='right'caption='[[1l0c]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1l0c]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ovis_ammon_aries Ovis ammon aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L0C OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1L0C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1l0c]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L0C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L0C FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COT:COA-S-ACETYL+TRYPTAMINE'>COT</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]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1b6b|1b6b]], [[1cjw|1cjw]], [[1bo4|1bo4]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COT:COA-S-ACETYL+TRYPTAMINE'>COT</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AANAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9940 Ovis ammon aries])</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=1l0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l0c OCA], [https://pdbe.org/1l0c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l0c RCSB], [https://www.ebi.ac.uk/pdbsum/1l0c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l0c ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aralkylamine_N-acetyltransferase Aralkylamine N-acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.87 2.3.1.87] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1l0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l0c OCA], [http://pdbe.org/1l0c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1l0c RCSB], [http://www.ebi.ac.uk/pdbsum/1l0c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1l0c ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SNAT_SHEEP 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.<ref>PMID:15644438</ref> | + | [https://www.uniprot.org/uniprot/SNAT_SHEEP 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.<ref>PMID:15644438</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aralkylamine N-acetyltransferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ovis ammon aries]] | + | [[Category: Ovis aries]] |
| - | [[Category: Angelis, J De]]
| + | [[Category: Burley SK]] |
| - | [[Category: Burley, S K]] | + | [[Category: Cole PA]] |
| - | [[Category: Cole, P A]] | + | [[Category: De Angelis J]] |
| - | [[Category: Scheibner, K A]] | + | [[Category: Scheibner KA]] |
| - | [[Category: Alternate conformation]] | + | |
| - | [[Category: Bisubstrate analog]]
| + | |
| - | [[Category: Enzyme-inhibitor complex]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
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.[1]
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
Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase (AANAT)) is a critical enzyme in the light-mediated regulation of melatonin production and circadian rhythm. It is a member of the GNAT (GCN-5-related N-acetyltransferase) superfamily of enzymes, which catalyze a diverse array of biologically important acetyl transfer reactions from antibiotic resistance to chromatin remodeling. In this study, we probed the functional properties of two histidines (His-120 and His-122) and a tyrosine (Tyr-168) postulated to be important in the mechanism of AANAT based on prior x-ray structural and biochemical studies. Using a combination of steady-state kinetic measurements of microviscosity effects and pH dependence on the H122Q, H120Q, and H120Q/H122Q AANAT mutants, we show that His-122 (with an apparent pK(a) of 7.3) contributes approximately 6-fold to the acetyltransferase chemical step as either a remote catalytic base or hydrogen bond donor. Furthermore, His-120 and His-122 appear to contribute redundantly to this function. By analysis of the Y168F AANAT mutant, it was demonstrated that Tyr-168 contributes approximately 150-fold to the acetyltransferase chemical step and is responsible for the basic limb of the pH-rate profile with an apparent (subnormal) pK(a) of 8.5. Paradoxically, Y168F AANAT showed 10-fold enhanced apparent affinity for acetyl-CoA despite the loss of a hydrogen bond between the Tyr phenol and the CoA sulfur atom. The X-ray crystal structure of Y168F AANAT bound to a bisubstrate analog inhibitor showed no significant structural perturbation of the enzyme compared with the wild-type complex, but revealed the loss of dual inhibitor conformations present in the wild-type complex. Taken together with kinetic measurements, these crystallographic studies allow us to propose the relevant structural conformations related to the distinct alkyltransferase and acetyltransferase reactions catalyzed by AANAT. These findings have significant implications for understanding GNAT catalysis and the design of potent and selective inhibitors.
Investigation of the roles of catalytic residues in serotonin N-acetyltransferase.,Scheibner KA, De Angelis J, Burley SK, Cole PA J Biol Chem. 2002 May 17;277(20):18118-26. Epub 2002 Mar 7. PMID:11884405[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ganguly S, Weller JL, Ho A, Chemineau P, Malpaux B, Klein DC. Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1222-7. Epub 2005 Jan 11. PMID:15644438 doi:0406871102
- ↑ Scheibner KA, De Angelis J, Burley SK, Cole PA. Investigation of the roles of catalytic residues in serotonin N-acetyltransferase. J Biol Chem. 2002 May 17;277(20):18118-26. Epub 2002 Mar 7. PMID:11884405 doi:10.1074/jbc.M200595200
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