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.

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.

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

MeSH terms

  • Adenosine Diphosphate Ribose / chemistry
  • Adenosine Diphosphate Ribose / metabolism*
  • Catalytic Domain
  • Crystallography, X-Ray / methods*
  • DNA Repair Enzymes / chemistry*
  • DNA Repair Enzymes / metabolism*
  • Humans
  • Hydrolases / chemistry*
  • Hydrolases / metabolism*
  • Hydrolysis
  • Protein Binding
  • Protein Conformation
  • Protein Domains

Substances

  • MACROD2 protein, human
  • Adenosine Diphosphate Ribose
  • Hydrolases
  • DNA Repair Enzymes