Mortensen Sofia, Kuncová Stanislava, Lormand Justin D, Myers Tanner M, Kim Soo-Kyoung, Lee Vincent T, Winkler Wade C, Sondermann Holger
CSSB Centre for Structural Systems Biology, Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607 Hamburg, Germany.
Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
Nucleic Acids Res. 2025 Jan 7;53(1). doi: 10.1093/nar/gkae1235.
Dinucleases of the DEDD superfamily, such as oligoribonuclease, Rexo2 and nanoRNase C, catalyze the essential final step of RNA degradation, the conversion of di- to mononucleotides. The active sites of these enzymes are optimized for substrates that are two nucleotides long, and do not discriminate between RNA and DNA. Here, we identified a novel DEDD subfamily, members of which function as dedicated deoxydinucleases (diDNases) that specifically hydrolyze single-stranded DNA dinucleotides in a sequence-independent manner. Crystal structures of enzyme-substrate complexes reveal that specificity for DNA stems from a combination of conserved structural elements that exclude diribonucleotides as substrates. Consistently, diDNases fail to complement the loss of enzymes that act on diribonucleotides, indicating that these two groups of enzymes support distinct cellular functions. The genes encoding diDNases are found predominantly in genomic islands of Actinomycetes and Clostridia, which, together with their association with phage-defense systems, suggest potential roles in bacterial immunity.
DEDD超家族的二核酸酶，如寡核糖核酸酶、Rexo2和纳米核糖核酸酶C，催化RNA降解的关键最后一步，即二核苷酸向单核苷酸的转化。这些酶的活性位点针对两个核苷酸长的底物进行了优化，并且不区分RNA和DNA。在这里，我们鉴定了一个新的DEDD亚家族，其成员作为专门的脱氧二核酸酶（二脱氧核酸酶）发挥作用，以序列非依赖的方式特异性水解单链DNA二核苷酸。酶-底物复合物的晶体结构表明，对DNA的特异性源于保守结构元件的组合，这些元件排除了双核糖核苷酸作为底物。一致地，二脱氧核酸酶无法弥补作用于双核糖核苷酸的酶的缺失，表明这两组酶支持不同的细胞功能。编码二脱氧核酸酶的基因主要存在于放线菌和梭菌的基因组岛中，这与它们与噬菌体防御系统的关联一起，暗示了它们在细菌免疫中的潜在作用。
