Abstract
The electron paramagnetic resonance spectra of purified neuronal nitric oxide synthase indicates that the binding of ligands to the arginine site perturbs the environment of the high-spin ferriheme in a highly ligand-specific manner. Four categories of high-spin complex can be distinguished; all are five-coordinate, and all retain the axial thiolate ligand, but they differ in their ligation geometries. These spectroscopic species reveal distinct local conformations which can be stabilized individually by the binding of L-arginine, N omega-hydroxy-L-arginine, N omega-methyl-L-arginine, and N omega-nitro-L-arginine. Other arginine analog inhibitors stabilize one or more of these states, revealing patterns based on the nature of substituents at the terminal amino group.
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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Animals
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Arginine / analogs & derivatives
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Arginine / metabolism*
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Arginine / pharmacology
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Binding Sites
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Cell Line
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Citrulline / pharmacology
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Electron Spin Resonance Spectroscopy
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology
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Heme / chemistry
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Heme / metabolism*
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Kidney
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Neurons / enzymology*
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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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Nitroarginine
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Ornithine / analogs & derivatives
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Ornithine / metabolism
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Rats
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omega-N-Methylarginine
Substances
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Enzyme Inhibitors
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Nitroarginine
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omega-N-Methylarginine
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Citrulline
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N(G)-iminoethylornithine
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N(5)-hydroxy-L-arginine
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Heme
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Arginine
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Ornithine
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Nitric Oxide Synthase