Journal:Acta Cryst F:S2053230X20011309

Multiple crystal forms of human MacroD2

Sarah Wazir, Mirko M. Maksimainen and Lari Lehtiö ^[1]

Molecular Tour
MacroD2 is one of the three human macrodomain proteins characterized for their protein linked mono-ADP-ribosyl-hydrolyzing activity. MacroD2 is a single domain protein containing a deep ADP-ribose binding groove. In this study new crystallization conditions for MacroD2 were found and three crystal structures of human MacroD2 in apo state were solved in space groups P4₁2₁2, P4₃2₁2 and P4₃ and refined at 1.75, 1.90 and 1.70 Å resolutions, respectively. Structural comparison of the apo crystal structures to the previously reported MacroD2 crystal structure in complex with ADP-ribose revealed conformational changes in the side chains of Val101, Ile189 and Phe224 induced by the binding of ADP-ribose into the active site. These conformational variations may potentially facilitate design efforts of a MacroD2 inhibitor.

Ribbon representations of the secondary structures of apo MacroD2 in:

• (PDB ID 6y4y, chain A) (light blue).
• (PDB ID 6y4z, chain A) (warm pink).
• (PDB ID 6y73, chain A) (salmon).

• . Secondary structures of P4₁2₁2 (PDB ID 6y4y), P4₃2₁2 (PDB ID 6y4z), and P4₃ (PDB ID 6y73) are coloured as light blue, warm pink and salmon, respectively.

References

1. ↑ Wazir S, Maksimainen MM, Lehtio L. Multiple crystal forms of human MacroD2. Acta Crystallogr F Struct Biol Commun. 2020 Oct 1;76(Pt 10):477-482. doi:, 10.1107/S2053230X20011309. Epub 2020 Sep 15. PMID:33006575 doi:http://dx.doi.org/10.1107/S2053230X20011309