Dimerization of the plant molybdenum insertase Cnx1E is required for synthesis of the molybdenum cofactor

Biochem J. 2017 Jan 1;474(1):163-178. doi: 10.1042/BCJ20160846. Epub 2016 Nov 1.

Abstract

The molybdenum cofactor (Moco) is a redox active prosthetic group, essentially required for numerous enzyme-catalyzed two electron transfer reactions. Moco is synthesized by an evolutionarily old and highly conserved multistep pathway. In the last step of Moco biosynthesis, the molybdenum center is inserted into the final Moco precursor adenylated molybdopterin (MPT-AMP). This unique and yet poorly characterized maturation reaction finally yields physiologically active Moco. In the model plant Arabidopsis, the two domain enzyme, Cnx1, is required for Moco formation. Recently, a genetic screen identified novel Arabidopsis cnx1 mutant plant lines each harboring a single amino acid exchange in the N-terminal Cnx1E domain. Biochemical characterization of the respective recombinant Cnx1E variants revealed two different amino acid exchanges (S197F and G175D) that impair Cnx1E dimerization, thus linking Cnx1E oligomerization to Cnx1 functionality. Analysis of the Cnx1E structure identified Cnx1E active site-bound molybdate and magnesium ions, which allowed to fine-map the Cnx1E MPT-AMP-binding site.

Keywords: Mo-insertase; molybdenum cofactor maturation; molybdenum cofactor synthesis.

MeSH terms

  • Amino Acid Substitution
  • Arabidopsis Proteins* / chemistry
  • Arabidopsis Proteins* / genetics
  • Arabidopsis Proteins* / metabolism
  • Arabidopsis* / chemistry
  • Arabidopsis* / genetics
  • Arabidopsis* / metabolism
  • Calnexin* / chemistry
  • Calnexin* / genetics
  • Calnexin* / metabolism
  • Catalytic Domain
  • Coenzymes / chemistry
  • Coenzymes / genetics
  • Coenzymes / metabolism
  • Metalloproteins / chemistry
  • Metalloproteins / genetics
  • Metalloproteins / metabolism
  • Molybdenum Cofactors
  • Mutation, Missense
  • Protein Multimerization / physiology*
  • Protein Structure, Secondary
  • Pteridines / chemistry
  • Pteridines / metabolism

Substances

  • Arabidopsis Proteins
  • CNX1 protein, Arabidopsis
  • Coenzymes
  • Metalloproteins
  • Molybdenum Cofactors
  • Pteridines
  • Calnexin
  • molybdenum cofactor