|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Guanine-specific ADP-ribosyltransferase== | | ==Guanine-specific ADP-ribosyltransferase== |
| - | <StructureSection load='5zj4' size='340' side='right' caption='[[5zj4]], [[Resolution|resolution]] 1.50Å' scene=''> | + | <StructureSection load='5zj4' size='340' side='right'caption='[[5zj4]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zj4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Strco Strco]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZJ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZJ4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zj4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_coelicolor_A3(2) Streptomyces coelicolor A3(2)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZJ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZJ4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4973928Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SCO5461 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=100226 STRCO])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5zj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zj4 OCA], [http://pdbe.org/5zj4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zj4 RCSB], [http://www.ebi.ac.uk/pdbsum/5zj4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zj4 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5zj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zj4 OCA], [https://pdbe.org/5zj4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zj4 RCSB], [https://www.ebi.ac.uk/pdbsum/5zj4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zj4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SCARP_STRCO SCARP_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).<ref>PMID:23212047</ref> <ref>PMID:30072382</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Strco]] | + | [[Category: Large Structures]] |
| - | [[Category: Tsuge, H]] | + | [[Category: Tsuge H]] |
| - | [[Category: Yoshida, T]] | + | [[Category: Yoshida T]] |
| - | [[Category: Adp-ribosyltransferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
SCARP_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 PubMed
ScARP 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
- ↑ Nakano T, Matsushima-Hibiya Y, Yamamoto M, Takahashi-Nakaguchi A, Fukuda H, Ono M, Takamura-Enya T, Kinashi H, Totsuka Y. ADP-ribosylation of guanosine by SCO5461 protein secreted from Streptomyces coelicolor. Toxicon. 2013 Mar 1;63:55-63. PMID:23212047 doi:10.1016/j.toxicon.2012.11.019
- ↑ Yoshida T, Tsuge H. Substrate N(2) atom recognition mechanism in pierisin family DNA-targeting guanine-specific ADP-ribosyltransferase ScARP. J Biol Chem. 2018 Aug 2. pii: AC118.004412. doi: 10.1074/jbc.AC118.004412. PMID:30072382 doi:http://dx.doi.org/10.1074/jbc.AC118.004412
- ↑ Yoshida T, Tsuge H. Substrate N(2) atom recognition mechanism in pierisin family DNA-targeting guanine-specific ADP-ribosyltransferase ScARP. J Biol Chem. 2018 Aug 2. pii: AC118.004412. doi: 10.1074/jbc.AC118.004412. PMID:30072382 doi:http://dx.doi.org/10.1074/jbc.AC118.004412
|
