Sirtuin 5: a review of structure, known inhibitors and clues for developing new inhibitors

Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylases, which regulate important biological processes ranging from apoptosis, age-associated pathophysiologies, adipocyte and muscle differentiation, and energy expenditure to gluconeogenesis. Very recently, sirtuin 5 (SIRT5) has received considerable attention due to that it was found to have weak deacetylase activity but strong desuccinylase, demalonylase and deglutarylase activities, and it was also found to be associated with several human diseases such as cancer, Alzheimer's disease, and Parkinson's disease. In this review, we for the first time summarized the structure characteristics, known peptide and small-molecule inhibitors of SIRT5, extracted some clues from current available information and introduced some feasible, practical in silico methods, which might be useful in further efforts to develop new SIRT5 inhibitors.