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. Author manuscript; available in PMC: 2012 Dec 1.
Published in final edited form as: Nat Struct Mol Biol. 2012 May 20;19(6):653–656. doi: 10.1038/nsmb.2305

Figure 3.

Figure 3

The mammalian PARG structure supports endo-glycosidic cleavage of poly(ADP-ribose). (a) Sequence alignments of rat PARG, human PARG8, macrodomain Af152112, macrodomain D115, macrodomain H2A1.113, and T. curvata glycohydrolase14 reveal unique C-terminal helices (α13 and α14) in mammalian PARG that pack against α12. Interacting residues of α12, α13, and α14 of rat PARG are labeled with black dots (•. (b) The 2′-OH of ADP-HPD is exposed in the rPARG385 structure (orange) to enable binding and internal cleavage of PAR polymers by endo-glycohydrolase activity. One of three representative (n+1) ADP-ribose conformers from panel (c) is shown as a stick model (black). Residues from the S7-H5 loop ofthe T. curvata glycohydrolase (white) cap the ribose ring, limiting binding activity to the terminal ADP-ribose of a PAR substrate for exo-glycohydrolase activity. (c) Comparison of solvent accessible surfaces reveals an open platform in rat PARG (left) that can accommodate the (n+1) ADP-ribose, whereas the 2′-OH of the adenosine ribose is completely blocked by the ribose cap in the T. curvata glycohydrolase (right). Three representative (n+1) ADP-ribose conformers from computational simulations are shown in rat PARG surface.