Structural highlights
Function
[SIR5_DANRE] NAD-dependent lysine demalonylase and desuccinylase that specifically removes malonyl and succinyl groups on target proteins. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo (By similarity).
Publication Abstract from PubMed
Sirtuins are protein deacylases that regulate metabolism and stress responses and are implicated in aging-related diseases. Modulators of the human sirtuins Sirt1-7 are sought as chemical tools and potential therapeutics, e.g., for cancer. Selective and potent inhibitors are available for Sirt2, but selective inhibitors for Sirt5 with Ki values in the low nanomolar range are lacking. We synthesized and screened 3-arylthiosuccinylated and 3-benzylthiosuccinylated peptide derivatives yielding Sirt5 inhibitors with low-nanomolar Ki values. A biotinylated derivative with this scaffold represents an affinity probe for human Sirt5 that is able to selectively extract this enzyme out of complex biological samples like cell lysates. Crystal structures of Sirt5/inhibitor complexes reveal that the compounds bind in an unexpected manner to the active site of Sirt5.
Potent and Selective Inhibitors of Human Sirtuin 5.,Kalbas D, Liebscher S, Nowak T, Meleshin M, Pannek M, Popp C, Alhalabi Z, Bordusa F, Sippl W, Steegborn C, Schutkowski M J Med Chem. 2018 Mar 12. doi: 10.1021/acs.jmedchem.7b01648. PMID:29494161[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kalbas D, Liebscher S, Nowak T, Meleshin M, Pannek M, Popp C, Alhalabi Z, Bordusa F, Sippl W, Steegborn C, Schutkowski M. Potent and Selective Inhibitors of Human Sirtuin 5. J Med Chem. 2018 Mar 12. doi: 10.1021/acs.jmedchem.7b01648. PMID:29494161 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b01648
