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Gramicidin channel controversy — reply

Nature Structural Biology volume 6, pages 611–612 (1999)Cite this article

Cross et al. and Andersen et al. object to our recent suggestion1 that the active conformation of gramicidin A may be the double-stranded double-helical (DS) dimer structure instead of the more traditional head-to-head single-stranded dimer (SS) model. They present literature evidence that supports their model. We would like to explain the rationale for our proposal.

It is true that Arseniev et al.2 first described the DS dimer observed by us in our CsCl crystal structure. Although we cited a reference to the NMR determination of the structure of the gramicidin cesium complex in methanol/chloroform solution, it was a refinement of the original work of Arseniev by Nekrasov, Stepanova and Timofeeva. We acknowledge our error in failing to acknowledge the original2. However, no coordinates of that structure have ever been deposited in the Protein Data Bank and it was not possible to perform a detailed comparison with the findings. More important in this discussion is the fact that our structure challenges the accuracy of the Cs+ gramicidin structure report by Wallace and Ravikumar3. That structure has crystallographic, stereochemical, and chemical anomalies and its coordinates and diffraction data have never been made public. Additional anomalies appear in the KSCN bound gramicidin A structure published by Doyle and Wallace4. In an effort to replicate the work of Wallace we used nearly identical crystallization conditions and grew crystals having the same space group and cell dimensions. However, our structures, based upon much higher resolution data sets, differ in every detail with those of Wallace and have none of the crystallographic, stereochemical or chemical anomolies of their structures. It is also noteworthy that while there is complete agreement between the structure of Cs+ complex in methanol/chloroform reported by Arseniev and our crystal structure, we are aware of no state of the art NMR solution data that unequivocally supports the Wallace structure. Consequently we question the validity of the Wallace structures.

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  1. Molecular Biophysics Department, Hauptman-Woodward Medical Research Institute, 73 High Street, Buffalo, 14203, New York, USA

    Brian M. Burkhart & William L. Duax

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  1. Brian M. Burkhart
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  2. William L. Duax
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Burkhart, B., Duax, W. Gramicidin channel controversy — reply. Nat Struct Mol Biol 6, 611–612 (1999). https://doi.org/10.1038/10652

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