5bwn: Difference between revisions

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== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/SIR3_HUMAN 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.<ref>PMID:16788062</ref> <ref>PMID:18680753</ref> <ref>PMID:18794531</ref> <ref>PMID:19535340</ref>   
[[http://www.uniprot.org/uniprot/SIR3_HUMAN 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.<ref>PMID:16788062</ref> <ref>PMID:18680753</ref> <ref>PMID:18794531</ref> <ref>PMID:19535340</ref>   
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== Publication Abstract from PubMed ==
SIRT1-7 play important roles in many biological processes and age-related diseases. In addition to a NAD(+) -dependent deacetylase activity, they can catalyze several other reactions, including the hydrolysis of long-chain fatty acyl lysine. To study the binding modes of sirtuins to long-chain acyl lysines, we solved the crystal structures of SIRT3 bound to either a H3K9-myristoylated- or a H3K9-palmitoylated peptide. Interaction of SIRT3 with the palmitoyl group led to unfolding of the alpha3-helix. The myristoyl and palmitoyl groups bind to the C-pocket and an allosteric site near the alpha3-helix, respectively. We found that the residues preceding the alpha3-helix determine the size of the C-pocket. The flexibility of the alpha2-alpha3 loop and the plasticity of the alpha3-helix affect the interaction with long-chain acyl lysine.
Crystal structures of SIRT3 reveal that the alpha2-alpha3 loop and alpha3-helix affect the interaction with long-chain acyl lysine.,Gai W, Li H, Jiang H, Long Y, Liu D FEBS Lett. 2016 Sep;590(17):3019-28. doi: 10.1002/1873-3468.12345. Epub 2016 Aug , 24. PMID:27501476<ref>PMID:27501476</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5bwn" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Revision as of 22:41, 9 December 2016

Crystal Structure of SIRT3 with a H3K9 Peptide Containing a Myristoyl LysineCrystal Structure of SIRT3 with a H3K9 Peptide Containing a Myristoyl Lysine

Structural highlights

5bwn is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
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

SIRT1-7 play important roles in many biological processes and age-related diseases. In addition to a NAD(+) -dependent deacetylase activity, they can catalyze several other reactions, including the hydrolysis of long-chain fatty acyl lysine. To study the binding modes of sirtuins to long-chain acyl lysines, we solved the crystal structures of SIRT3 bound to either a H3K9-myristoylated- or a H3K9-palmitoylated peptide. Interaction of SIRT3 with the palmitoyl group led to unfolding of the alpha3-helix. The myristoyl and palmitoyl groups bind to the C-pocket and an allosteric site near the alpha3-helix, respectively. We found that the residues preceding the alpha3-helix determine the size of the C-pocket. The flexibility of the alpha2-alpha3 loop and the plasticity of the alpha3-helix affect the interaction with long-chain acyl lysine.

Crystal structures of SIRT3 reveal that the alpha2-alpha3 loop and alpha3-helix affect the interaction with long-chain acyl lysine.,Gai W, Li H, Jiang H, Long Y, Liu D FEBS Lett. 2016 Sep;590(17):3019-28. doi: 10.1002/1873-3468.12345. Epub 2016 Aug , 24. PMID:27501476[5]

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

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ Gai W, Li H, Jiang H, Long Y, Liu D. Crystal structures of SIRT3 reveal that the alpha2-alpha3 loop and alpha3-helix affect the interaction with long-chain acyl lysine. FEBS Lett. 2016 Sep;590(17):3019-28. doi: 10.1002/1873-3468.12345. Epub 2016 Aug , 24. PMID:27501476 doi:http://dx.doi.org/10.1002/1873-3468.12345

5bwn, resolution 1.94Å

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