Abstract
Two crystal structures of recombinant Geobacillus stearothermophilus 6-phosphogluconate dehydrogenase (Gs6PDH) in complex with the substrate 6-phosphogluconate have been determined at medium resolution. Gs6PDH shares significant sequence identity and structural similarity with the enzymes from Lactococcus lactis, sheep liver and the protozoan parasite Trypanosoma brucei,
for which a range of structures have previously been reported.
Comparisons indicate that amino-acid sequence conservation is more
pronounced in the two domains that contribute to the architecture of the
active site, namely the N-terminal and C-terminal domains, compared
with the central domain, which is primarily involved in the
subunit-subunit associations required to form a stable dimer. The
active-site residues are highly conserved, as are the interactions with
the 6-phosphogluconate. There is interest in 6PDH as a potential drug
target for the protozoan parasite T. brucei, the pathogen responsible for African sleeping sickness. The recombinant T. brucei
enzyme has proven to be recalcitrant to enzyme-ligand studies and a
surrogate protein might offer new opportunities to investigate and
characterize 6PDH inhibitors. The high degree of structural similarity,
efficient level of expression and straightforward crystallization
conditions mean that Gs6PDH may prove to be an appropriate model system for structure-based inhibitor design targeting the enzyme from Trypanosoma species.
Original language | English |
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Pages (from-to) | 450-454 |
Number of pages | 5 |
Journal | Acta Crystallographica Section F: Structural Biology and Crystallization Communications |
Volume | 65 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2009 |
Externally published | Yes |
Keywords
- Pentose phosphate pathway
- 6-phosphogluconate dehydrogenase
- Geobacillus stearothermophilus