1kuv: Difference between revisions
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==X-ray Crystallographic Studies of Serotonin N-acetyltransferase Catalysis and Inhibition== | ==X-ray Crystallographic Studies of Serotonin N-acetyltransferase Catalysis and Inhibition== | ||
<StructureSection load='1kuv' size='340' side='right' caption='[[1kuv]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='1kuv' size='340' side='right'caption='[[1kuv]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1kuv]] 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=1KUV OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[1kuv]] 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=1KUV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1KUV FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA5:COA-S-ACETYL+5-BROMOTRYPTAMINE'>CA5</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA5:COA-S-ACETYL+5-BROMOTRYPTAMINE'>CA5</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bo4|1bo4]], [[1b6b|1b6b]], [[1cjw|1cjw]], [[1kux|1kux]], [[1kuy|1kuy]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1bo4|1bo4]], [[1b6b|1b6b]], [[1cjw|1cjw]], [[1kux|1kux]], [[1kuy|1kuy]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">U29663 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9940 Ovis ammon aries])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">U29663 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9940 Ovis ammon aries])</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='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:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1kuv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kuv OCA], [http://pdbe.org/1kuv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1kuv RCSB], [http://www.ebi.ac.uk/pdbsum/1kuv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1kuv ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ku/1kuv_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ku/1kuv_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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</div> | </div> | ||
<div class="pdbe-citations 1kuv" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1kuv" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Serotonin N-acetyltransferase|Serotonin N-acetyltransferase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Aralkylamine N-acetyltransferase]] | [[Category: Aralkylamine N-acetyltransferase]] | ||
[[Category: Large Structures]] | |||
[[Category: Ovis ammon aries]] | [[Category: Ovis ammon aries]] | ||
[[Category: Angelis, J De]] | [[Category: Angelis, J De]] | ||
Revision as of 10:50, 25 November 2020
X-ray Crystallographic Studies of Serotonin N-acetyltransferase Catalysis and InhibitionX-ray Crystallographic Studies of Serotonin N-acetyltransferase Catalysis and Inhibition
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 PubMedThe structure of serotonin N-acetyltransferase (also known as arylalkylamine N-acetyltransferase; AANAT) bound to a potent bisubstrate analog inhibitor has been determined at 2.0 A resolution using a two-edge (Se, Br) multiwavelength anomalous diffraction (MAD) experiment. This acetyl-CoA dependent enzyme is a member of the GCN5-related family of N-acetyltransferases (GNATs), which share four conserved sequence motifs (A-D). In serotonin N-acetyltransferase, motif A adopts an alpha/beta conformation characteristic of the phylogenetically invariant cofactor binding site seen in all previously characterized GNATs. Motif B displays a significantly lower level of conservation among family members, giving rise to a novel alpha/beta structure for the serotonin binding slot. Utilization of a brominated CoA-S-acetyl-tryptamine-bisubstrate analog inhibitor and the MAD method permitted conclusive identification of two radically different conformations for the tryptamine moiety in the catalytic site (cis and trans). A second high-resolution X-ray structure of the enzyme bound to a bisubstrate analog inhibitor, with a longer tether between the acetyl-CoA and tryptamine moieties, demonstrates only the trans conformation. Given a previous proposal that AANAT can catalyze an alkyltransferase reaction in a conformationally altered active site relative to its acetyltransferase activity, it is possible that the two conformations of the bisubstrate analog observed crystallographically correspond to these alternative reaction pathways. Our findings may ultimately lead to the design of analogs with improved AANAT inhibitory properties for in vivo applications. X-ray crystallographic studies of serotonin N-acetyltransferase catalysis and inhibition.,Wolf E, De Angelis J, Khalil EM, Cole PA, Burley SK J Mol Biol. 2002 Mar 22;317(2):215-24. PMID:11902838[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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