Sauve Anthony A
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10065, USA.
Biochim Biophys Acta. 2010 Aug;1804(8):1591-603. doi: 10.1016/j.bbapap.2010.01.021. Epub 2010 Feb 2.
Sirtuins are ancient proteins widely distributed in all lifeforms of earth. These proteins are universally able to bind NAD(+), and activate it to effect ADP-ribosylation of cellular nucleophiles. The most commonly observed sirtuin reaction is the ADP-ribosylation of acetyllysine, which leads to NAD(+)-dependent deacetylation. Other types of ADP-ribosylation have also been observed, including protein ADP-ribosylation, NAD(+) solvolysis and ADP-ribosyltransfer to 5,6-dimethylbenzimidazole, a reaction involved in eubacterial cobalamin biosynthesis. This review broadly surveys the chemistries and chemical mechanisms of these enzymes.
沉默调节蛋白是广泛分布于地球上所有生命形式中的古老蛋白质。这些蛋白质普遍能够结合烟酰胺腺嘌呤二核苷酸(NAD⁺),并激活它以实现细胞亲核试剂的ADP核糖基化。最常见的沉默调节蛋白反应是乙酰赖氨酸的ADP核糖基化,这会导致依赖NAD⁺的去乙酰化。还观察到了其他类型的ADP核糖基化,包括蛋白质ADP核糖基化、NAD⁺溶剂解以及ADP核糖基转移至5,6 - 二甲基苯并咪唑,这是一种参与真细菌钴胺素生物合成的反应。本综述广泛概述了这些酶的化学性质和化学机制。