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Toxicon : official journal of the International Society on Toxinology

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


PMID 23212047

Abstract

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 110xa0μM. SCO5461 was further found to ADP-ribosylate deoxyguanosine, GMP, dGMP, GTP, dGTP, and cyclic GMP with k(cat) values of 150-370xa0s(-1). Oligo(dG), oligo(G), and yeast tRNA were also ADP-ribosylated by this protein, although with much lower k(cat) values of 0.2xa0s(-1) or less. SCO5461 showed maximum ADP-ribosylation activity towards guanosine at 30xa0°C, and maintained 20% of these maximum activity levels even at 0xa0°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.