The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate

Mol Cell. 2001 Oct;8(4):829-39. doi: 10.1016/s1097-2765(01)00372-0.


More than 50 human proteins with a wide range of functions have a 120 residue phosphoinositide binding module known as the PX domain. The 1.7 A X-ray crystal structure of the PX domain from the p40(phox) subunit of NADPH oxidase bound to PtdIns(3)P shows that the PX domain embraces the 3-phosphate on one side of a water-filled, positively charged pocket and reveals how 3-phosphoinositide specificity is achieved. A chronic granulomatous disease (CGD)-associated mutation in the p47(phox) PX domain that abrogates PtdIns(3)P binding maps to a conserved Arg that does not directly interact with the phosphoinositide but instead appears to stabilize a critical lipid binding loop. The SH3 domain present in the full-length protein does not affect soluble PtdIns(3)P binding to the p40(phox) PX domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Calorimetry
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • NADPH Oxidases / chemistry
  • Phosphatidylinositol Phosphates / chemistry
  • Phosphatidylinositol Phosphates / metabolism*
  • Phosphoproteins / chemistry*
  • Phosphoproteins / metabolism
  • Protein Binding
  • Protein Structure, Tertiary*
  • Protein Subunits
  • Sequence Alignment
  • Ultracentrifugation


  • Phosphatidylinositol Phosphates
  • Phosphoproteins
  • Protein Subunits
  • neutrophil cytosol factor 40K
  • phosphatidylinositol 3-phosphate
  • NADPH Oxidases