Multiple crystal forms of human MacroD2

DOI: 10.1107/S2053230X20011309

Authors: Sarah Wazir (University of Oulu) , Mirko M. Maksimainen (University of Oulu) , Lari Lehtiö (University of Oulu)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section F Structural Biology Communications , VOL 76 , PAGES 477 - 482

State: Published (Approved)
Published: October 2020
Diamond Proposal Number(s): 19951

Abstract: 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 P41212, P43212 and P43, 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.

Journal Keywords: macrodomain; ADP-ribosylation; ADP-ribosyl-hydrolase; crystal forms; apo structure

Subject Areas: Biology and Bio-materials


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Other Facilities: ID23-1 at ESRF