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Author

Cho, Moo Je
Ulsan National Institute of Science and Technology
Research Interests
  • Calcium Signaling

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A point mutation in a plant calmodulin is responsible for its inhibition of nitric-oxide synthase

Cited 33 times inthomson ciCited 33 times inthomson ci
Title
A point mutation in a plant calmodulin is responsible for its inhibition of nitric-oxide synthase
Author
Kondo, RTikunova, SBCho, Moo JeJohnson, JD
Keywords
ELECTRON-TRANSFER; CYCLIC-GMP; BINDING DOMAIN; ACTIVATION; CALCINEURIN; CALCIUM; MUTANTS; ISOFORM; SIGNAL; MUSCLE
Issue Date
199912
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.274, no.51, pp.36213 - 36218
Abstract
The calcium/calmodulin-dependent activation of nitric-oxide synthase (NOS) and its production of nitric oxide (NO) play a key regulatory role in plant and animal cell function. SCaM-1 is a plant calmodulin (CaM) isoform that is 91% identical to mammalian CaM (wild type CaM (wtCaM)) and a selective competitive antagonist of NOS (Cho, M. J., Vaghy, P. L., Kondo, R., Lee, S. H., Davis, J. P., Rehl, R., Heo, W. D., and Johnson, J. D. (1998) Biochemistry 37, 15593-15597), We have used site-directed mutagenesis to show that a point mutation, involving the substitution of valine for methionine at position 144, is responsible for SCaM-1's inhibition of mammalian NOS. An M144V mutation in wild type CaM produced a mutant (M144V) which exhibited nearly identical inhibition of NOS's NO production and NADPH oxidation, with a similar K-i (similar to 15 nM) as SCaM-1, A V144M back mutation in SCaM-1 significantly restored its ability to activate NOS's catalytic functions. The length of the hydrophobic amino acid side chain at position 144 appears to be critical for NOS activation, since M144L and M144F activated NOS while M144V and M144C did not. Despite their competitive antagonism of NOS, M144V, like SCaM-1, exhibited a similar dose-dependent activation of phosphodiesterase and calcineurin as wtCaM. SCaM-1 and M144V produced greater inhibition of NOS's oxygenase domain function (NO production) than its reductase domain functions (NADPH oxidation and cytochrome c reduction). Thus, CaM's methionine 144 plays a critical role the activation of NOS, presumably by influencing the function of NOS's oxygenase domain.
URI
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DOI
http://dx.doi.org/10.1074/jbc.274.51.36213
ISSN
0021-9258
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