5zj4
From Proteopedia
Guanine-specific ADP-ribosyltransferase
Structural highlights
FunctionSCARP_STRCO ADP-ribosylates the N2 amino group of guanosine, deoxyguanosine, GMP, dGMP, cGMP, GTP and dGTP; oligo-guanosine, oligo-deoxyguanosine and tRNA are ADP-ribosylated less efficiently, while dsDNA is a very poor substrate (PubMed:23212047). Also acts on GDP (PubMed:30072382).[1] [2] Publication Abstract from PubMedScARP from the bacterium Streptomyces coelicolor belongs to the pierisin family of DNA-targeting ADP-ribosyltransferases (ARTs). These enzymes ADP-ribosylate the N(2) amino groups of guanine residues in DNA to yield N(2)-(ADP-ribos-1-yl)-2'-deoxyguanosine. Although the structures of pierisin-1 and Scabin were revealed recently, the substrate recognition mechanisms remain poorly understood because of the lack of a substrate-binding structure. Here, we report the apo structure of ScARP and of ScARP bound to NADH and its GDP substrate at 1.50 and 1.57 A resolutions, respectively. The bound structure revealed that the guanine of GDP is trapped between N-ribose of NADH and Trp159. Interestingly, N(2) and N(3) of guanine formed hydrogen bonds with the OE1 and NE2 atoms of Gln162, respectively. We directly observed that the ADP-ribosylating toxin turn-turn (ARTT)-loop including Trp159 and Gln162 plays a key role in the specificity of DNA-targeting guanine-specific ART as well as protein-targeting ARTs such as C3 exoenzyme. We propose that the ARTT-loop recognition is a common substrate recognition mechanism in the pierisin family. Furthermore, this complex structure sheds light on similarities and differences among two subclasses that are distinguished by conserved structural motifs: H-Y-E in the ARTD subfamily and R-S-E in the ARTC subfamily. The spatial arrangements of the electrophile and nucleophile were the same, providing the first evidence for a common reaction mechanism in these ARTs. ARTC (including ScARP) uses the ARTT-loop for substrate recognition, whereas ARTD (represented by Arr) uses the C-terminal helix instead of the ARTT-loop. These observations could help inform efforts to improve ART inhibitors. Substrate N(2) atom recognition mechanism in pierisin family DNA-targeting guanine-specific ADP-ribosyltransferase ScARP.,Yoshida T, Tsuge H J Biol Chem. 2018 Aug 2. pii: AC118.004412. doi: 10.1074/jbc.AC118.004412. PMID:30072382[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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