4r8m

From Proteopedia

(Difference between revisions)

Revision as of 17:21, 18 January 2017

Human SIRT2 crystal structure in complex with BHJH-TM1

Structural highlights

4r8m is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3pkj, 3zgo, 3zgv, 4l3o
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SIR2_HUMAN] NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and non-histone proteins. Deacetylates 'Lys-40' of alpha-tubulin. Involved in the control of mitotic exit in the cell cycle, probably via its role in the regulation of cytoskeleton. Deacetylates PCK1, opposing proteasomal degradation. Deacetylates 'Lys-310' of RELA.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Sirtuins are a class of enzymes originally identified as nicotinamide adenine dinucleotide (NAD)-dependent protein lysine deacetylases. Among the seven mammalian sirtuins, SIRT1-7, only SIRT1-3 possess efficient deacetylase activity in vitro, whereas SIRT4-7 possess very weak in vitro deacetylase activity. Several sirtuins that exhibit weak deacetylase activity have recently been shown to possess more efficient activity for the removal other acyl lysine modifications, such as succinyl lysine and palmitoyl lysine. Here, we demonstrate that even the well-known deacetylase SIRT2 possesses efficient activity for the removal of long-chain fatty acyl groups. The catalytic efficiency (kcat/Km) for the removal of a myristoyl group is slightly higher than that for the removal of an acetyl group. The crystal structure of SIRT2 in complex with a thiomyristoyl peptide reveals that SIRT2 possesses a large hydrophobic pocket that can accommodate the myristoyl group. Comparison of the SIRT2 acyl pocket to those of SIRT1, SIRT3, and SIRT6 reveals that the acyl pockets of SIRT1-3 are highly similar, and to a lesser degree, similar to that of SIRT6. The efficient in vitro demyristoylase activity of SIRT2 suggests that this activity may be physiologically relevant and warrants future investigative studies.

Efficient Demyristoylase Activity of SIRT2 Revealed by Kinetic and Structural Studies.,Teng YB, Jing H, Aramsangtienchai P, He B, Khan S, Hu J, Lin H, Hao Q Sci Rep. 2015 Feb 23;5:8529. doi: 10.1038/srep08529. PMID:25704306^[5]

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

References

↑ North BJ, Marshall BL, Borra MT, Denu JM, Verdin E. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell. 2003 Feb;11(2):437-44. PMID:12620231
↑ Dryden SC, Nahhas FA, Nowak JE, Goustin AS, Tainsky MA. Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. Mol Cell Biol. 2003 May;23(9):3173-85. PMID:12697818
↑ Rothgiesser KM, Erener S, Waibel S, Luscher B, Hottiger MO. SIRT2 regulates NF-kappaB dependent gene expression through deacetylation of p65 Lys310. J Cell Sci. 2010 Dec 15;123(Pt 24):4251-8. doi: 10.1242/jcs.073783. Epub 2010 Nov, 16. PMID:21081649 doi:10.1242/jcs.073783
↑ Jiang W, Wang S, Xiao M, Lin Y, Zhou L, Lei Q, Xiong Y, Guan KL, Zhao S. Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Mol Cell. 2011 Jul 8;43(1):33-44. doi: 10.1016/j.molcel.2011.04.028. PMID:21726808 doi:10.1016/j.molcel.2011.04.028
↑ Teng YB, Jing H, Aramsangtienchai P, He B, Khan S, Hu J, Lin H, Hao Q. Efficient Demyristoylase Activity of SIRT2 Revealed by Kinetic and Structural Studies. Sci Rep. 2015 Feb 23;5:8529. doi: 10.1038/srep08529. PMID:25704306 doi:http://dx.doi.org/10.1038/srep08529

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/4r8m"

@@ Line 1: / Line 1: @@
 ==Human SIRT2 crystal structure in complex with BHJH-TM1==
 <StructureSection load='4r8m' size='340' side='right' caption='[[4r8m]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3LX:TRIDECANETHIAL'>3LX</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">[[3pkj|3pkj]], [[3zgo|3zgo]], [[3zgv|3zgv]], [[4l3o|4l3o]]</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=4r8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r8m RCSB], [http://www.ebi.ac.uk/pdbsum/4r8m PDBsum]</span></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=4r8m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8m OCA], [http://pdbe.org/4r8m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r8m RCSB], [http://www.ebi.ac.uk/pdbsum/4r8m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r8m ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4r8m" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Histone deacetylase|Histone deacetylase]]
 == References ==
 <references/>

4r8m

From Proteopedia

Revision as of 17:21, 18 January 2017

Human SIRT2 crystal structure in complex with BHJH-TM1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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