2h2g: Difference between revisions
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==The Structural Basis of Sirtuin substrate affinity== | ==The Structural Basis of Sirtuin substrate affinity== | ||
<StructureSection load='2h2g' size='340' side='right' caption='[[2h2g]], [[Resolution|resolution]] 1.63Å' scene=''> | <StructureSection load='2h2g' size='340' side='right'caption='[[2h2g]], [[Resolution|resolution]] 1.63Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2h2g]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2h2g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C] and [https://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H2G FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.63Å</td></tr> | ||
<tr><td class="sblockLbl"><b>[[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2h2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h2g OCA], [https://pdbe.org/2h2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h2g RCSB], [https://www.ebi.ac.uk/pdbsum/2h2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h2g ProSAT]</span></td></tr> | |||
<tr | </table> | ||
== Function == | |||
<table> | [https://www.uniprot.org/uniprot/NPD_THEMA NPD_THEMA] NAD-dependent protein deacetylase which modulates the activities of several enzymes which are inactive in their acetylated form. Has also depropionylation activity in vitro. Also able to ADP-ribosylate peptide substrates with Arg or Lys in the +2 position. The role of this function in vivo is not clear.<ref>PMID:17684016</ref> <ref>PMID:16905097</ref> <ref>PMID:19801667</ref> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h2/2h2g_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h2/2h2g_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2h2g ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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The structural basis of sirtuin substrate affinity.,Cosgrove MS, Bever K, Avalos JL, Muhammad S, Zhang X, Wolberger C Biochemistry. 2006 Jun 20;45(24):7511-21. PMID:16768447<ref>PMID:16768447</ref> | The structural basis of sirtuin substrate affinity.,Cosgrove MS, Bever K, Avalos JL, Muhammad S, Zhang X, Wolberger C Biochemistry. 2006 Jun 20;45(24):7511-21. PMID:16768447<ref>PMID:16768447</ref> | ||
From | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2h2g" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae S288C]] | |||
[[Category: Thermotoga maritima]] | [[Category: Thermotoga maritima]] | ||
[[Category: Cosgrove | [[Category: Cosgrove MS]] | ||
[[Category: Wolberger | [[Category: Wolberger C]] | ||
Latest revision as of 11:06, 30 October 2024
The Structural Basis of Sirtuin substrate affinityThe Structural Basis of Sirtuin substrate affinity
Structural highlights
FunctionNPD_THEMA NAD-dependent protein deacetylase which modulates the activities of several enzymes which are inactive in their acetylated form. Has also depropionylation activity in vitro. Also able to ADP-ribosylate peptide substrates with Arg or Lys in the +2 position. The role of this function in vivo is not clear.[1] [2] [3] 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 PubMedSirtuins comprise a family of enzymes that catalyze the deacetylation of acetyllysine side chains in a reaction that consumes NAD+. Although several crystal structures of sirtuins bound to non-native acetyl peptides have been determined, relatively little about how sirtuins discriminate among different substrates is understood. We have carried out a systematic structural and thermodynamic analysis of several peptides bound to a single sirtuin, the Sir2 homologue from Thermatoga maritima (Sir2Tm). We report structures of five different forms of Sir2Tm: two forms bound to the p53 C-terminal tail in the acetylated and unacetylated states, two forms bound to putative acetyl peptide substrates derived from the structured domains of histones H3 and H4, and one form bound to polypropylene glycol (PPG), which resembles the apoenzyme. The structures reveal previously unobserved complementary side chain interactions between Sir2Tm and the first residue N-terminal to the acetyllysine (position -1) and the second residue C-terminal to the acetyllysine (position +2). Isothermal titration calorimetry was used to compare binding constants between wild-type and mutant forms of Sir2Tm and between additional acetyl peptide substrates with substitutions at positions -1 and +2. The results are consistent with a model in which peptide positions -1 and +2 play a significant role in sirtuin substrate binding. This model provides a framework for identifying sirtuin substrates. The structural basis of sirtuin substrate affinity.,Cosgrove MS, Bever K, Avalos JL, Muhammad S, Zhang X, Wolberger C Biochemistry. 2006 Jun 20;45(24):7511-21. PMID:16768447[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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