2nyr

File:2nyr.gif

spinqualitylabelsall models 2nyr, resolution 2.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 with SVR and ZN as ligands. This structure superseeds 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

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