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

C. S. Raman, Huiying Li, Pavel Martásek, Vladimir Král, Bettie Sue S. Masters, Thomas L. Poulos

Research output: Contribution to journalArticlepeer-review

559 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)939-950
Number of pages12
JournalCell
Volume95
Issue number7
DOIs
StatePublished - Dec 23 1998

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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