Abstract
The crystal structure of the endothelial nitric oxide synthase (NOS) heme domain complexed with NO reveals close hydrogen bonding interactions between NO and the terminal guanidino nitrogen of the substrate, L-arginine. Dioxygen is expected to bind in a similar mode which will facilitate proton abstraction from L-Arg to dioxygen, a required step for O-O bond cleavage. Structures of mechanism-based NOS inhibitors, N(5)-(1-iminoethyl)-L-ornithine and N-(3-(aminomethyl)benzyl)acetamidine, provide clues on how this class of compounds operate as suicide substrate inhibitors leading to heme oxidation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amidines / chemistry
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Amidines / metabolism
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Animals
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Benzylamines / chemistry
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Benzylamines / metabolism
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Binding, Competitive
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Cattle
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Crystallography, X-Ray
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / metabolism
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Ferrous Compounds / chemistry
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Heme / chemistry
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / chemistry
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Isoenzymes / metabolism
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Macromolecular Substances
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Nitric Oxide / chemistry*
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Nitric Oxide / metabolism
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Nitric Oxide Synthase / antagonists & inhibitors*
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Nitric Oxide Synthase / chemistry*
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type III
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Ornithine / analogs & derivatives
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Ornithine / chemistry
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Ornithine / metabolism
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Protein Structure, Tertiary
Substances
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Amidines
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Benzylamines
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Enzyme Inhibitors
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Ferrous Compounds
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Isoenzymes
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Macromolecular Substances
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N-(3-(aminomethyl)benzyl)acetamidine
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Nitric Oxide
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N(G)-iminoethylornithine
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Heme
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Ornithine
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type III
Associated data
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PDB/1ED6
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PDB/1FOI
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PDB/1FOL
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PDB/1FOO
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PDB/1FOP