2nyr: Difference between revisions

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Revision as of 18:52, 20 March 2008

File:2nyr.gif

, resolution 2.06Å

Ligands:

and

Gene:

SIRT5, SIR2L5 (Homo sapiens)

Coordinates:

save as pdb, mmCIF, xml

Crystal Structure of Human Sirtuin Homolog 5 in Complex with Suramin

OverviewOverview

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.

About this StructureAbout this Structure

2NYR is a Single protein structure of sequence from Homo sapiens. This structure supersedes the now removed PDB entry 2FZQ. Full crystallographic information is available from OCA.

ReferenceReference

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

Page seeded by OCA on Thu Mar 20 17:52:56 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2nyr.gif|left|200px]]<br /><applet load="2nyr" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2nyr.gif|left|200px]]
-caption="2nyr, resolution 2.06&Aring;" />
-'''Crystal Structure of Human Sirtuin Homolog 5 in Complex with Suramin'''<br />
+ {{Structure
+|PDB= 2nyr |SIZE=350|CAPTION= <scene name='initialview01'>2nyr</scene>, resolution 2.06&Aring;
+|SITE=
+|LIGAND= <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> and <scene name='pdbligand=ZN:ZINC ION'>ZN</scene>
+|ACTIVITY=
+|GENE= SIRT5, SIR2L5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+}}
+'''Crystal Structure of Human Sirtuin Homolog 5 in Complex with Suramin'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-NYR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SVR:'>SVR</scene> and <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 2FZQ. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NYR OCA].
+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 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://ispc.weizmann.ac.il//pmbin/getpm?pmid=17355872 17355872]
+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]]
@@ Line 29: / Line 38: @@
 [[Category: hydrolase]]
 [[Category: sgc]]
-[[Category: structural genomics]]
+[[Category: structural genomic]]
 [[Category: structural genomics consortium]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:12:36 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:52:56 2008''