Inosine 5'-monophosphate dehydrogenase binds nucleic acids in vitro and in vivo

Biochem J. 2004 Apr 15;379(Pt 2):243-51. doi: 10.1042/BJ20031585.


Inosine 5'-monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in the de novo biosynthesis of guanine nucleotides. In addition to the catalytic domain, IMPDH contains a subdomain of unknown function composed of two cystathione beta-synthase domains. Our results, using three different assays, show that IMPDHs from Tritrichomonas foetus, Escherichia coli, and both human isoforms bind single-stranded nucleic acids with nanomolar affinity via the subdomain. Approx. 100 nucleotides are bound per IMPDH tetramer. Deletion of the subdomain decreases affinity 10-fold and decreases site size to 60 nucleotides, whereas substitution of conserved Arg/Lys residues in the subdomain with Glu decreases affinity by 20-fold. IMPDH is found in the nucleus of human cells, as might be expected for a nucleic-acid-binding protein. Lastly, immunoprecipitation experiments show that IMPDH binds both RNA and DNA in vivo. These experiments indicate that IMPDH has a previously unappreciated role in replication, transcription or translation that is mediated by the subdomain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Cell Nucleus / enzymology
  • DNA / metabolism*
  • DNA, Single-Stranded / metabolism
  • Humans
  • IMP Dehydrogenase / analysis
  • IMP Dehydrogenase / chemistry
  • IMP Dehydrogenase / metabolism*
  • Nucleic Acids / chemistry
  • Nucleic Acids / metabolism
  • Nucleic Acids / pharmacology
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA / metabolism*
  • Ultraviolet Rays


  • DNA, Single-Stranded
  • Nucleic Acids
  • RNA
  • DNA
  • IMP Dehydrogenase