ADP-ribosylation of guanosine by SCO5461 protein secreted from Streptomyces coelicolor

作者：Nakano Tsuyoshi^*; Matsushima Hibiya Yuko; Yamamoto Masafumi; Takahashi Nakaguchi Azusa; Fukuda Hirokazu; Ono Masaya; Takamura Enya Takeji; Kinashi Haruyasu; Totsuka Yukari

来源：Toxicon, 2013, 63: 55-63.

DOI：10.1016/j.toxicon.2012.11.019

• Actinomycete
• ADP-ribosylation
• Modified bases

The Streptomyces coelicolor A3(2) genome encodes a possible secretion protein, SCO5461, that shares a 30% homology with the activity domains of two toxic ADP-ribosyltransferases, pierisins and mosquitocidal toxin. We found ADP-ribosylating activity for the SCO5461 protein product through its co-incubation with guanosine and NAD(+), which resulted in the formation of N-2-(ADP-ribos-1-yl)-guanosine ((ar2)Guo), with a K-m value of 110 mu M. SCO5461 was further found to ADP-ribosylate deoxyguanosine, GMP, dGMP, GTP, dGTP, and cyclic GMP with k(cat) values of 150-370 s(-1). Oligo(dG), oligo(G), and yeast tRNA were also ADP-ribosylated by this protein, although with much lower k(cat) values of 0.2 s(-1) less. SCO5461 showed maximum ADP-ribosylation activity towards guanosine at 30 degrees C, and maintained 20% of these maximum activity levels even at 0 degrees C. This is the first report of the ADP-ribosylation of guanosine and guanine mononucleotides among the family members of various ADP-ribosylating enzymes. We additionally observed secretion of the putative gene product, SCO5461, in liquid cultures of S. coelicolor. We thus designated the SCO5461 protein product as S. coelicolor ADP-ribosylating protein, ScARP. Our current results could offer new insights into not only the ADP-ribosylation of small molecules but also signal transduction events via enzymatic nucleoside modification by toxin-related enzymes.

• 出版日期2013-3-1