Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
Science. 2011 Nov 11;334(6057):806-9. doi: 10.1126/science.1207861.
Silent information regulator 2 (Sir2) proteins (sirtuins) are nicotinamide adenine dinucleotide-dependent deacetylases that regulate important biological processes. Mammals have seven sirtuins, Sirt1 to Sirt7. Four of them (Sirt4 to Sirt7) have no detectable or very weak deacetylase activity. We found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro. The preference for succinyl and malonyl groups was explained by the presence of an arginine residue (Arg(105)) and tyrosine residue (Tyr(102)) in the acyl pocket of Sirt5. Several mammalian proteins were identified with mass spectrometry to have succinyl or malonyl lysine modifications. Deletion of Sirt5 in mice appeared to increase the level of succinylation on carbamoyl phosphate synthase 1, which is a known target of Sirt5. Thus, protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo.
沉默信息调节因子 2（Sir2）蛋白（sirtuins）是烟酰胺腺嘌呤二核苷酸依赖性去乙酰化酶，可调节重要的生物学过程。哺乳动物有七种 sirtuins，Sirt1 到 Sirt7。其中四个（Sirt4 到 Sirt7）没有检测到或非常弱的去乙酰化酶活性。我们发现 Sirt5 在体外是一种有效的蛋白质赖氨酸脱琥珀酰基和脱丙二酰基酶。在 Sirt5 的酰基口袋中存在精氨酸残基（Arg（105））和酪氨酸残基（Tyr（102）），这解释了对琥珀酰基和丙二酰基的偏好。通过质谱法鉴定了几种哺乳动物蛋白，这些蛋白具有琥珀酰基或丙二酰基赖氨酸修饰。在小鼠中删除 Sirt5 似乎增加了氨基甲酰磷酸合成酶 1 上的琥珀酰化水平，氨基甲酰磷酸合成酶 1 是 Sirt5 的已知靶标。因此，蛋白质赖氨酸琥珀酰化可能代表一种翻译后修饰，可被体内的 Sirt5 逆转。
