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

Acta Crystallogr D Struct Biol. 2017 Jul 1;73(Pt 7):609-617. doi: 10.1107/S2059798317007677. Epub 2017 Jun 28.


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.

Keywords: MarathonMR; contaminant; glycerol dehydrogenase; molecular replacement; serendipity.

MeSH terms

  • Bacterial Proteins / chemistry*
  • Crystallization / methods*
  • Crystallography, X-Ray / methods*
  • Models, Molecular
  • Protein Conformation
  • Salmonella typhimurium / chemistry*
  • Sugar Alcohol Dehydrogenases / chemistry*


  • Bacterial Proteins
  • Sugar Alcohol Dehydrogenases
  • glycerol dehydrogenase