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    Loss of Conformational Stability in Calmodulin upon Methionine Oxidation

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    SchoeneichC_BJ_73(3)1115.pdf (496.7Kb)
    Issue Date
    1998-03
    Author
    Gao, Jun
    Yin, Daniel H.
    Yao, Yihong
    Sun, Hongye
    Qin, Zhihai
    Schoeneich, Christian
    Williams, Todd D.
    Squier, Thomas C.
    Publisher
    Cell Press
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
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    Abstract
    We have used electrospray ionization mass spectrometry (ESI-MS), circular dichroism (CD), and fluorescence spectroscopy to investigate the secondary and tertiary structural consequences that result from oxidative modification of methionine residues in wheat germ calmodulin (CaM), and prevent activation of the plasma membrane Ca-ATPase. Using ESI-MS, we have measured rates of modification and molecular mass distributions of oxidatively modified CaM species (CaMox) resulting from exposure to H2O2. From these rates, we find that oxidative modification of methionine to the corresponding methionine sulfoxide does not predispose CaM to further oxidative modification. These results indicate that methionine oxidation results in no large-scale alterations in the tertiary structure of CaMox, because the rates of oxidative modification of individual methionines are directly related to their solvent exposure. Likewise, CD measurements indicate that methionine oxidation results in little change in the apparent α-helical content at 28°C, and only a small (0.3 ± 0.1 kcal mol−1) decrease in thermal stability, suggesting the disruption of a limited number of specific noncovalent interactions. Fluorescence lifetime, anisotropy, and quenching measurements of N-(1-pyrenyl)-maleimide (PMal) covalently bound to Cys26 indicate local structural changes around PMal in the amino-terminal domain in response to oxidative modification of methionine residues in the carboxyl-terminal domain. Because the opposing globular domains remain spatially distant in both native and oxidatively modified CaM, the oxidative modification of methionines in the carboxyl-terminal domain are suggested to modify the conformation of the amino-terminal domain through alterations in the structural features involving the interdomain central helix. The structural basis for the linkage between oxidative modification and these global conformational changes is discussed in terms of possible alterations in specific noncovalent interactions that have previously been suggested to stabilize the central helix in CaM.
    URI
    http://hdl.handle.net/1808/17757
    DOI
    https://doi.org/10.1016/S0006-3495(98)77830-0
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    • Pharmaceutical Chemistry Scholarly Works [340]
    Citation
    Gao et al. "Loss of Conformational Stability in Calmodulin upon Methionine Oxidation." Biophysical Journal Volume 74, Issue 3, March 1998, Pages 1115–1134. http://dx.doi.org/10.1016/S0006-3495(98)77830-0

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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