4g1c

From Proteopedia

(Difference between revisions)

Current revision

Human SIRT5 bound to Succ-IDH2 and Carba-NAD

Structural highlights

4g1c is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.944Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Carba-NAD is a synthetic compound identical to NAD except for one substitution, where an oxygen atom adjacent to the anomeric linkage bearing nicotinamide is replaced with a methylene group. Because it is inert in nicotinamide displacement reactions, carba-NAD is an unreactive substrate analogue for NAD consuming enzymes. SIRT3 and SIRT5 are NAD consuming enzymes that are potential therapeutic targets for the treatment of metabolic diseases and cancers. We report an improved carba-NAD synthesis, including a pyrophosphate coupling method that proceeds in approximately 60% yield. We also disclose the x-ray crystal structures of the ternary complexes of SIRT3 and SIRT5 bound to a peptide substrate and carba-NAD. These x-ray crystal structures provide critical snapshots of the mechanism by which human sirtuins function as protein deacylation catalysts.

Synthesis of Carba-NAD and the Structures of Its Ternary Complexes with SIRT3 and SIRT5.,Szczepankiewicz BG, Dai H, Koppetsch KJ, Qian D, Jiang F, Mao C, Perni RB J Org Chem. 2012 Jul 31. PMID:22849721^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker CF, Steegborn C. Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J Mol Biol. 2008 Oct 10;382(3):790-801. doi: 10.1016/j.jmb.2008.07.048. Epub 2008, Jul 25. PMID:18680753 doi:10.1016/j.jmb.2008.07.048
↑ Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, Tan M, Luo H, Zhang Y, He W, Yang K, Zwaans BM, Tishkoff D, Ho L, Lombard D, He TC, Dai J, Verdin E, Ye Y, Zhao Y. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol Cell Proteomics. 2011 Dec;10(12):M111.012658. doi: 10.1074/mcp.M111.012658., Epub 2011 Sep 9. PMID:21908771 doi:http://dx.doi.org/10.1074/mcp.M111.012658
↑ Lin ZF, Xu HB, Wang JY, Lin Q, Ruan Z, Liu FB, Jin W, Huang HH, Chen X. SIRT5 desuccinylates and activates SOD1 to eliminate ROS. Biochem Biophys Res Commun. 2013 Nov 8;441(1):191-5. doi:, 10.1016/j.bbrc.2013.10.033. Epub 2013 Oct 16. PMID:24140062 doi:http://dx.doi.org/10.1016/j.bbrc.2013.10.033
↑ Du J, Zhou Y, Su X, Yu JJ, Khan S, Jiang H, Kim J, Woo J, Kim JH, Choi BH, He B, Chen W, Zhang S, Cerione RA, Auwerx J, Hao Q, Lin H. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science. 2011 Nov 11;334(6057):806-9. PMID:22076378 doi:10.1126/science.1207861
↑ Szczepankiewicz BG, Dai H, Koppetsch KJ, Qian D, Jiang F, Mao C, Perni RB. Synthesis of Carba-NAD and the Structures of Its Ternary Complexes with SIRT3 and SIRT5. J Org Chem. 2012 Jul 31. PMID:22849721 doi:10.1021/jo301067e

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4g1c"

Categories: Homo sapiens | Large Structures | Dai H

@@ Line 1: / Line 1: @@
 ==Human SIRT5 bound to Succ-IDH2 and Carba-NAD==
-<StructureSection load='4g1c' size='340' side='right' caption='[[4g1c]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
+<StructureSection load='4g1c' size='340' side='right'caption='[[4g1c]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4g1c]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G1C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G1C FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4g1c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G1C FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CNA:CARBA-NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>CNA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.944&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SLL:(2S)-2-AZANYL-6-[(4-HYDROXY-4-OXO-BUTANOYL)AMINO]HEXANOIC+ACID'>SLL</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CNA:CARBA-NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>CNA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SLL:(2S)-2-AZANYL-6-[(4-HYDROXY-4-OXO-BUTANOYL)AMINO]HEXANOIC+ACID'>SLL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fvt|4fvt]]</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=4g1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g1c OCA], [https://pdbe.org/4g1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g1c RCSB], [https://www.ebi.ac.uk/pdbsum/4g1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g1c ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SIRT5, SIR2L5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4g1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g1c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4g1c RCSB], [http://www.ebi.ac.uk/pdbsum/4g1c PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4g1c" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 24: / Line 24: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Dai, H]]
+[[Category: Large Structures]]
-[[Category: Carbanad]]
+[[Category: Dai H]]
-[[Category: Hydrolase]]
-[[Category: Sirtuin]]
-[[Category: Succinylated peptide]]

4g1c

From Proteopedia

Current revision

Human SIRT5 bound to Succ-IDH2 and Carba-NAD

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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