Crystal structure of a bifunctional transformylase and cyclohydrolase enzyme in purine biosynthesis

Nat Struct Biol. 2001 May;8(5):402-6. doi: 10.1038/87555.


ATIC, the product of the purH gene, is a 64 kDa bifunctional enzyme that possesses the final two activities in de novo purine biosynthesis, AICAR transformylase and IMP cyclohydrolase. The crystal structure of avian ATIC has been determined to 1.75 A resolution by the MAD method using a Se-methionine modified enzyme. ATIC forms an intertwined dimer with an extensive interface of approximately 5,000 A(2) per monomer. Each monomer is composed of two novel, separate functional domains. The N-terminal domain (up to residue 199) is responsible for the IMPCH activity, whereas the AICAR Tfase activity resides in the C-terminal domain (200-593). The active sites of the IMPCH and AICAR Tfase domains are approximately 50 A apart, with no structural evidence of a tunnel connecting the two active sites. The crystal structure of ATIC provides a framework to probe both catalytic mechanisms and to design specific inhibitors for use in cancer chemotherapy and inflammation.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Birds*
  • Crystallography, X-Ray
  • Dimerization
  • Hydroxymethyl and Formyl Transferases / chemistry*
  • Hydroxymethyl and Formyl Transferases / metabolism
  • Models, Molecular
  • Multienzyme Complexes / chemistry*
  • Multienzyme Complexes / metabolism
  • Nucleotide Deaminases / chemistry*
  • Nucleotide Deaminases / metabolism
  • Protein Structure, Tertiary
  • Purines / biosynthesis*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Structure-Activity Relationship


  • Multienzyme Complexes
  • Purines
  • Recombinant Fusion Proteins
  • inosine monophosphate synthase
  • Hydroxymethyl and Formyl Transferases
  • Nucleotide Deaminases
  • IMP cyclohydrolase

Associated data

  • PDB/1G8M