The functional principle of eukaryotic molybdenum insertases

Biochem J. 2018 May 24;475(10):1739-1753. doi: 10.1042/BCJ20170935.


The molybdenum cofactor (Moco) is a redox-active prosthetic group found in the active site of Moco-dependent enzymes, which are vitally important for life. Moco biosynthesis involves several enzymes that catalyze the subsequent conversion of GTP into cyclic pyranopterin monophosphate (cPMP), molybdopterin (MPT), adenylated MPT (MPT-AMP), and finally Moco. While the underlying principles of cPMP, MPT, and MPT-AMP formation are well understood, the molybdenum insertase (Mo-insertase)-catalyzed final Moco maturation step is not. In the present study, we analyzed high-resolution X-ray datasets of the plant Mo-insertase Cnx1E that revealed two molybdate-binding sites within the active site, hence improving the current view on Cnx1E functionality. The presence of molybdate anions in either of these sites is tied to a distinctive backbone conformation, which we suggest to be essential for Mo-insertase molybdate selectivity and insertion efficiency.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Catalysis
  • Catalytic Domain
  • Coenzymes / chemistry
  • Coenzymes / metabolism*
  • Eukaryota / enzymology*
  • Metalloproteins / chemistry
  • Metalloproteins / genetics
  • Metalloproteins / metabolism*
  • Molybdenum / chemistry
  • Molybdenum / metabolism*
  • Molybdenum Cofactors
  • Mutation
  • Protein Conformation
  • Pteridines / chemistry
  • Pteridines / metabolism*
  • Sequence Homology


  • Coenzymes
  • Metalloproteins
  • Molybdenum Cofactors
  • Pteridines
  • Molybdenum
  • molybdenum cofactor