Crystal structure of constitutive endothelial nitric oxide synthase: A paradigm for pterin function involving a novel metal center

Academic Article

Abstract

  • Nitric oxide, a key signaling molecule, is produced by a family of enzymes collectively called nitric oxide synthases (NOS). Here, we report the crystal structure of the heme domain of endothelial NOS in tetrahydrobiopterin (H4B)-free and -bound forms at 1.95 Å and 1.9 Å resolution, respectively. In both structures a zinc ion is tetrahedrally coordinated to pairs of symmetry-related cysteine residues at the dimer interface. The phylogenetically conserved Cys-(X)4-Cys motif and its strategic location establish a structural role for the metal center in maintaining the integrity of the H4B-binding site. The unexpected recognition of the substrate, L-arginine, at the H4B site indicates that this site is poised to stabilize a positively charged pterin ring and suggests a model involving a cationic pterin radical in the catalytic cycle.
  • Authors

    Published In

  • Cell  Journal
  • Digital Object Identifier (doi)

    Author List

  • Raman CS; Li H; Martásek P; Král V; Masters BSS; Poulos TL
  • Start Page

  • 939
  • End Page

  • 950
  • Volume

  • 95
  • Issue

  • 7