Misadventures in Reciprocal Space

Transporters are not on the Christmas card list of your average Pharma scientist. They will pump your offerings out of the cells and compartments into which you would like them to go. They are, however, essential for normal physiological function and serve an important protective role.

At the start of the featured exchange we find The Blue Team in a strong defensive position with five publications (1 | 2 | 3 | 4 | 5), spanning four years, on the MsbA and EmrE transporters. The journals concerned have high impact factors and it would seem that all is quiet on the western front.

Maybe not that quiet and one should remember that the Maginot Line was truly formidable when viewed from an anterior perspective. The Red Team launches a well-prepared flanking manoeuvre. Their structure for Sav1866 looks rather different to that of The Blue Team’s MsbA . Sufficiently different to indicate a convergent evolution of the two proteins, provided of course that the differences are indeed real.

The front collapses in disarray and soon a white flag hangs forlornly at The Blue Team’s command post. An in-house data reduction program has introduced a sign change and the reported structures have the wrong hand. No doubt the shock troops of Open Source are saying, “We told you so!” but we just ask how the formidable Lady Bracknell would have loaded the orthonormal basis vectors of misfortune and carelessness.

Were there earlier signs of weakness in the defensive line? The Blue Team’s MsbA structure appears to be incompatible with disulfide cross-linking studies of P-gp. Shouldn’t be a problem because a crystallographic structure is fact and cross-linking studies are cross-linking studies. However, The Red Team acknowledge that their Sav1866 structure is consistent with these earlier cross-linking studies.

There are a number of lessons to be learned from this Cautionary Tale. Firstly, in using protein crystallography, there is a need to be able to separate fact, interpretation of fact and fiction. Secondly, one should not let journal impact factor get in the way of one’s critical thinking. And, lastly, The Blue Team sometimes comes second.