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Abstract：
Despite decades of research on ADP-ribosyltransferases (ARTs) from the poly(ADP-ribose) polymerase (PARP) family, one key aspect of these enzymes - their substrate specificity - has remained unclear. Here, we briefly discuss the history of this area and, more extensively, the recent breakthroughs, including the identification of protein serine residues as a major substrate of PARP1 and PARP2 in human cells and of cysteine and tyrosine as potential targets of specific PARPs. On the molecular level, the modification of serine residues requires a composite active site formed by PARP1 or PARP2 together with a specificity-determining factor, HPF1; this represents a new paradigm not only for PARPs but generally for post-translational modification (PTM) catalysis. Additionally, we discuss the identification of DNA as a substrate of PARP1, PARP2 and PARP3, and some bacterial ARTs and the discovery of noncanonical RNA capping by several PARP family members. Together, these recent findings shed new light on PARP-mediated catalysis and caution to \'expect the unexpected\' when it comes to further potential substrates.
摘要：
尽管对聚（ADP-核糖）聚合酶（PARP）家族的ADP-核糖基转移酶（ARTs）进行了数十年的研究，这些酶的一个关键方面-其底物特异性-仍不清楚。这里,我们简要讨论了这个地区的历史，更广泛的,最近的突破，包括鉴定蛋白丝氨酸残基作为人细胞中PARP1和PARP2的主要底物，以及半胱氨酸和酪氨酸作为特定PARP的潜在靶标。在分子水平上,丝氨酸残基的修饰需要由PARP1或PARP2形成的复合活性位点以及特异性决定因子，HPF1；这不仅代表了PARP的新范式，而且通常代表了翻译后修饰（PTM）催化的新范式。此外,我们讨论了DNA作为PARP1，PARP2和PARP3底物的鉴定，以及一些细菌ARTs，以及几个PARP家族成员发现的非规范RNA加帽。一起,这些最新发现为PARP介导的催化作用提供了新的思路，并在涉及更多潜在底物时警告“预期意外”。
