| 17552543 |
Brandau DT, Joshi SB, Smalter AM, Kim S, Steadman B, Middaugh CR: Stability of the Clostridium botulinum type A neurotoxin complex: an empirical phase diagram based approach. Mol Pharm. 2007 Jul-Aug;4(4):571-82. Epub 2007 Jun 7.
Clostridium botulinum type A neurotoxin (BoNT/A complex) is of great interest to the pharmaceutical industry. The drug itself is a natural complex of the toxin and a number of associated proteins. Surprisingly, relatively little is known about the exact structure and stability of the 900 kDa BoNT/A complex and its component proteins with the exception of the 150 kDa neurotoxin. In this study we describe the relative stability of the BoNT/A complex, the neurotoxin, and its associated proteins over a wide range of temperature and pH employing circular dichroism, intrinsic and 8-anilino-1-naphthalene sulfonate (ANS) fluorescence, and static light scattering. The data suggest a strong stabilizing effect of the associated proteins on the neurotoxin component. This data is compiled into empirical phase diagrams which permit the simultaneous visualization of multiple data sets over a wide range of conditions. |
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