Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Patent
1998-01-22
2000-08-15
Schwartzman, Robert A.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
530326, 530327, 530328, C07K 706, C07K 708, C07K 1447
Patent
active
061038725
ABSTRACT:
Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is important for N-methyl-D-aspartate (NMDA) receptor-dependent neurotransmitter release, neurotoxicity, and cyclic-GMP elevations. The coupling of NMDA receptor-mediated calcium influx and nNOS activation is postulated to be due to a physical coupling of the receptor and the enzyme by an intermediary adaptor protein PSD95, through a unique PDZ-PDZ domain interaction between PSD95 and nNOS. Here we report the identification of a novel nNOS associated protein, CAPON, which is highly enriched in brain and has numerous colocalizations with nNOS. CAPON interacts with the NNOS PDZ domain through its C-terminus. CAPON competes with PSD95 for interaction with nNOS, and overexpression of CAPON results in a loss of PSD95
NOS complexes in transfected cells. CAPON influences nNOS by regulating its ability to associate with PSD95/NMDA receptor complexes.
REFERENCES:
Jaffrey et al. "PIN: An Associated Protein Inhibitor of Neuronal Nitric Oxide Synthase" Science vol. 274, Nov. 1, 1996, pp. 774-777.
Brenman et al. "Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alphal-syntrophin mediated ny PDZ domains" Cell, vol. 84, Mar. 8, 1996, pp. 757-767.
Samie R. Jaffrey et al. "CAPON: A Protein Asociated with Neuronal Nitric Oxide Synthase that Regulates its Interactions with PSD95" Neuron, vol. 20, 115-124 Jan. 1998.
Jaffrey Samie R.
Snyder Solomon H.
Schwartzman Robert A.
The Johns Hopkins University
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