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@ARTICLE{Gierse:546331,
author = {Gierse, Robin M. and Reddem, Eswar R. and Alhayek, Alaa and
Baitinger, Dominik and Hamid, Zhoor and Jakobi, Harald and
Laber, Bernd and Lange, Gudrun and Hirsch, Anna K. H. and
Groves, Matthew},
title = {{I}dentification of a 1-deoxy-{D}-xylulose-5-phosphate
synthase ({DXS}) mutant with improved crystallographic
properties},
journal = {Biochemical and biophysical research communications},
volume = {539},
issn = {0006-291X},
address = {Orlando, Fla.},
publisher = {Academic Press},
reportid = {PUBDB-2023-00645},
pages = {42 - 47},
year = {2021},
abstract = {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.},
cin = {DOOR ; HAS-User},
ddc = {570},
cid = {I:(DE-H253)HAS-User-20120731},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3)},
pid = {G:(DE-HGF)POF4-6G3},
experiment = {EXP:(DE-H253)P-P11-20150101 / EXP:(DE-H253)P-P13-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33421767},
UT = {WOS:000613422000007},
doi = {10.1016/j.bbrc.2020.12.069},
url = {https://bib-pubdb1.desy.de/record/546331},
}