3d4b: Difference between revisions
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< | ==Crystal structure of Sir2Tm in complex with Acetyl p53 peptide and DADMe-NAD+== | ||
<StructureSection load='3d4b' size='340' side='right'caption='[[3d4b]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3d4b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D4B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D4B FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | |||
<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=DZD:5-O-[(R)-{[(R)-{[(3R,4R)-1-(3-CARBAMOYLBENZYL)-4-HYDROXYPYRROLIDIN-3-YL]METHOXY}(HYDROXY)PHOSPHORYL]METHYL}(HYDROXY)PHOSPHORYL]ADENOSINE'>DZD</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=3d4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d4b OCA], [https://pdbe.org/3d4b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d4b RCSB], [https://www.ebi.ac.uk/pdbsum/3d4b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d4b ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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 == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d4/3d4b_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</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/main_output.php?pdb_ID=3d4b ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Sirtuin enzymes comprise a unique class of NAD(+)-dependent protein deacetylases. Although structures of many sirtuin complexes have been determined, structural resolution of intermediate chemical steps are needed to understand the deacetylation mechanism. We report crystal structures of the bacterial sirtuin, Sir2Tm, in complex with an S-alkylamidate intermediate, analogous to the naturally occurring O-alkylamidate intermediate, and a Sir2Tm ternary complex containing a dissociated NAD(+) analog and acetylated peptide. The structures and biochemical studies reveal critical roles for the invariant active site histidine in positioning the reaction intermediate, and for a conserved phenylalanine residue in shielding reaction intermediates from base exchange with nicotinamide. The new structural and biochemical studies provide key mechanistic insight into intermediate steps of the Sir2 deacetylation reaction. | |||
Structural insights into intermediate steps in the Sir2 deacetylation reaction.,Hawse WF, Hoff KG, Fatkins DG, Daines A, Zubkova OV, Schramm VL, Zheng W, Wolberger C Structure. 2008 Sep 10;16(9):1368-77. PMID:18786399<ref>PMID:18786399</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3d4b" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
[[Category: | |||
[[Category: Thermotoga maritima]] | [[Category: Thermotoga maritima]] | ||
[[Category: Daines | [[Category: Daines A]] | ||
[[Category: Fatkins | [[Category: Fatkins D]] | ||
[[Category: Hawse | [[Category: Hawse WF]] | ||
[[Category: Hoff | [[Category: Hoff KG]] | ||
[[Category: Schramm | [[Category: Schramm VL]] | ||
[[Category: Wolberger | [[Category: Wolberger C]] | ||
[[Category: Zheng | [[Category: Zheng W]] | ||
[[Category: Zubkova | [[Category: Zubkova OV]] | ||
Latest revision as of 08:45, 17 October 2024
Crystal structure of Sir2Tm in complex with Acetyl p53 peptide and DADMe-NAD+Crystal structure of Sir2Tm in complex with Acetyl p53 peptide and DADMe-NAD+
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 PubMedSirtuin enzymes comprise a unique class of NAD(+)-dependent protein deacetylases. Although structures of many sirtuin complexes have been determined, structural resolution of intermediate chemical steps are needed to understand the deacetylation mechanism. We report crystal structures of the bacterial sirtuin, Sir2Tm, in complex with an S-alkylamidate intermediate, analogous to the naturally occurring O-alkylamidate intermediate, and a Sir2Tm ternary complex containing a dissociated NAD(+) analog and acetylated peptide. The structures and biochemical studies reveal critical roles for the invariant active site histidine in positioning the reaction intermediate, and for a conserved phenylalanine residue in shielding reaction intermediates from base exchange with nicotinamide. The new structural and biochemical studies provide key mechanistic insight into intermediate steps of the Sir2 deacetylation reaction. Structural insights into intermediate steps in the Sir2 deacetylation reaction.,Hawse WF, Hoff KG, Fatkins DG, Daines A, Zubkova OV, Schramm VL, Zheng W, Wolberger C Structure. 2008 Sep 10;16(9):1368-77. PMID:18786399[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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