Faculty of Biochemistry and Molecular Medicine, University of Oulu, PO Box 5400, Oulu 90014, Finland.
Acta Crystallogr F Struct Biol Commun. 2020 Oct 1;76(Pt 10):477-482. doi: 10.1107/S2053230X20011309. Epub 2020 Sep 15.
MacroD2 is one of the three human macrodomain proteins characterized by their protein-linked mono-ADP-ribosyl-hydrolyzing activity. MacroD2 is a single-domain protein that contains a deep ADP-ribose-binding groove. In this study, new crystallization conditions for MacroD2 were found and three crystal structures of human MacroD2 in the apo state were solved in space groups P422, P422 and P4, and refined at 1.75, 1.90 and 1.70 Å resolution, respectively. Structural comparison of the apo crystal structures with the previously reported crystal structure of MacroD2 in complex with ADP-ribose revealed conformational changes in the side chains of Val101, Ile189 and Phe224 induced by the binding of ADP-ribose in the active site. These conformational variations may potentially facilitate design efforts of a MacroD2 inhibitor.
MacroD2 是具有蛋白质连接单 ADP-核糖基水解活性的三种人类 Macrodomain 蛋白之一。MacroD2 是一种含有深 ADP-核糖结合槽的单结构域蛋白。在这项研究中，发现了 MacroD2 的新结晶条件，并解决了 apo 状态下人类 MacroD2 的三个晶体结构，分别在空间群 P422、P422 和 P4 中，分辨率分别为 1.75、1.90 和 1.70 Å。与先前报道的 MacroD2 与 ADP-核糖复合物的晶体结构进行结构比较，揭示了活性位点中 ADP-核糖结合引起的侧链 Val101、Ile189 和 Phe224 的构象变化。这些构象变化可能有助于 MacroD2 抑制剂的设计工作。
