2nyr: Difference between revisions

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-{{Seed}}
-[[Image:2nyr.png|left|200px]]
-<!--
+==Crystal Structure of Human Sirtuin Homolog 5 in Complex with Suramin==
-The line below this paragraph, containing "STRUCTURE_2nyr", creates the "Structure Box" on the page.
+<StructureSection load='2nyr' size='340' side='right'caption='[[2nyr]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2nyr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2fzq 2fzq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NYR FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.06&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SVR:8,8-[CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]]BIS-1,3,5-NAPHTHALENETRISULFONIC+ACID'>SVR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_2nyr|  PDB=2nyr  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2nyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nyr OCA], [https://pdbe.org/2nyr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nyr RCSB], [https://www.ebi.ac.uk/pdbsum/2nyr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nyr ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/SIR5_HUMAN SIR5_HUMAN] NAD-dependent lysine demalonylase and desuccinylase that specifically removes malonyl and succinyl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro.<ref>PMID:18680753</ref> <ref>PMID:21908771</ref> <ref>PMID:24140062</ref> <ref>PMID:22076378</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/ny/2nyr_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2nyr ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Sirtuins are NAD(+)-dependent protein deacetylases and are emerging as molecular targets for the development of pharmaceuticals to treat human metabolic and neurological diseases and cancer. To date, several sirtuin inhibitors and activators have been identified, but the structural mechanisms of how these compounds modulate sirtuin activity have not yet been determined. We identified suramin as a compound that binds to human SIRT5 and showed that it inhibits SIRT5 NAD(+)-dependent deacetylase activity with an IC(50) value of 22 microM. To provide insights into how sirtuin function is altered by inhibitors, we determined two crystal structures of SIRT5, one in complex with ADP-ribose, the other bound to suramin. Our structural studies provide a view of a synthetic inhibitory compound in a sirtuin active site revealing that suramin binds into the NAD(+), the product, and the substrate-binding site. Finally, our structures may enable the rational design of more potent inhibitors.
-===Crystal Structure of Human Sirtuin Homolog 5 in Complex with Suramin===
+Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin.,Schuetz A, Min J, Antoshenko T, Wang CL, Allali-Hassani A, Dong A, Loppnau P, Vedadi M, Bochkarev A, Sternglanz R, Plotnikov AN Structure. 2007 Mar;15(3):377-89. PMID:17355872<ref>PMID:17355872</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2nyr" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_17355872}}, adds the Publication Abstract to the page
+*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 17355872 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_17355872}}
+__TOC__
+</StructureSection>
-==About this Structure==
-NYR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2fzq 2fzq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NYR OCA].
-==Reference==
-Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin., Schuetz A, Min J, Antoshenko T, Wang CL, Allali-Hassani A, Dong A, Loppnau P, Vedadi M, Bochkarev A, Sternglanz R, Plotnikov AN, Structure. 2007 Mar;15(3):377-89. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17355872 17355872]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Allali-Hassani, A.]]
+[[Category: Allali-Hassani A]]
-[[Category: Antoshenko, T.]]
+[[Category: Antoshenko T]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Arrowsmith CH]]
-[[Category: Bochkarev, A.]]
+[[Category: Bochkarev A]]
-[[Category: Dong, A.]]
+[[Category: Dong A]]
-[[Category: Edwards, A M.]]
+[[Category: Edwards AM]]
-[[Category: Min, J R.]]
+[[Category: Min JR]]
-[[Category: Plotnikov, A N.]]
+[[Category: Plotnikov AN]]
-[[Category: SGC, Structural Genomics Consortium.]]
+[[Category: Sundstrom M]]
-[[Category: Sundstrom, M.]]
+[[Category: Weigelt J]]
-[[Category: Weigelt, J.]]
-[[Category: Histone deacetylase]]
-[[Category: Hydrolase]]
-[[Category: Sgc]]
-[[Category: Structural genomic]]
-[[Category: Structural genomics consortium]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 22:54:33 2008''