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4fvt

From Proteopedia

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Revision as of 07:40, 27 March 2019

Human SIRT3 bound to Ac-ACS peptide and Carba-NAD

Structural highlights

4fvt is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
NonStd Res:	,
Related:	4g1c
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SIR3_HUMAN] NAD-dependent protein deacetylase. Activates mitochondrial target proteins, including ACSS1, IDH2 and GDH by deacetylating key lysine residues. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels.^[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

↑ Schwer B, Bunkenborg J, Verdin RO, Andersen JS, Verdin E. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10224-9. Epub 2006 Jun 20. PMID:16788062 doi:10.1073/pnas.0603968103
↑ 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
↑ Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, Finkel T. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14447-52. doi:, 10.1073/pnas.0803790105. Epub 2008 Sep 15. PMID:18794531 doi:10.1073/pnas.0803790105
↑ Jin L, Wei W, Jiang Y, Peng H, Cai J, Mao C, Dai H, Choy W, Bemis JE, Jirousek MR, Milne JC, Westphal CH, Perni RB. Crystal structures of human SIRT3 displaying substrate-induced conformational changes. J Biol Chem. 2009 Sep 4;284(36):24394-405. Epub 2009 Jun 16. PMID:19535340 doi:10.1074/jbc.M109.014928
↑ 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 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Human SIRT3 bound to Ac-ACS peptide and Carba-NAD==
-<StructureSection load='4fvt' size='340' side='right' caption='[[4fvt]], [[Resolution|resolution]] 2.47&Aring;' scene=''>
+<StructureSection load='4fvt' size='340' side='right'caption='[[4fvt]], [[Resolution|resolution]] 2.47&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4fvt]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FVT FirstGlance]. <br>
@@ Line 28: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Dai, H]]
 [[Category: Carba-nad]]
 [[Category: Hydrolase]]
 [[Category: Sirtuin]]

4fvt

From Proteopedia

Revision as of 07:40, 27 March 2019

Human SIRT3 bound to Ac-ACS peptide and Carba-NAD

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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