Seeing but not believing: the structure of glycerol dehydrogenase initially assumed to be the structure of a survival protein from Salmonella typhimurium Salmonella typhimurium

摘要

The determination of the crystal structure of a mutant protein using phases based on a previously determined crystal structure of the wild‐type protein is often a straightforward molecular‐replacement protocol. Such a structure determination may be difficult if there are large‐scale structural differences between the wild‐type and mutant proteins. In this manuscript, an interesting case is presented of the unintentional crystallization of a contaminant protein which shared some structural features with the presumed target protein, leading to difficulties in obtaining a completely satisfactory molecular‐replacement structure solution. It was not immediately evident that the initial structure solution was incorrect owing to the poor quality of the X‐ray diffraction data and low resolution. The structure was subsequently determined by improving the quality of the data and following a sequence‐independent MarathonMR protocol. The structure corresponded to that of glycerol dehydrogenase, which crystallized as a contaminant, instead of the presumed mutant of a survival protein encoded by Salmonella typhimurium . The reasons why a solution that appeared to be reasonable was obtained with an incorrect protein model are discussed. The results presented here show that a degree of caution is warranted when handling large‐scale structure‐determination projects.