In this report, we describe a truncated Deinococcus radiodurans 1-deoxy-D-xylulose-5-phosphate synthase (DXS) protein that retains enzymatic activity, while slowing protein degradation and showing
improved crystallization properties. With modern drug-design approaches relying heavily on the
elucidation of atomic interactions of potential new drugs with their targets, the need for co-crystal
structures with the compounds of interest is high. DXS itself is a promising drug target, as it catalyzes
the first reaction in the 2-C-methyl-D-erythritol 4-phosphate (MEP)-pathway for the biosynthesis of the
universal precursors of terpenes, which are essential secondary metabolites. In contrast to many bacteria
and pathogens, which employ the MEP pathway, mammals use the distinct mevalonate-pathway for the
biosynthesis of these precursors, which makes all enzymes of the MEP-pathway potential new targets for
the development of anti-infectives. However, crystallization of DXS has proven to be challenging: while
the first X-ray structures from Escherichia coli and D. radiodurans were solved in 2004, since then only
two additions have been made in 2019 that were obtained under anoxic conditions. The presented site of
truncation can potentially also be transferred to other homologues, opening up the possibility for the
determination of crystal structures from pathogenic species, which until now could not be crystallized.
This manuscript also provides a further example that truncation of a variable region of a protein can lead
to improved structural data
