AI Article Synopsis
- The pentose phosphate pathway, particularly the enzyme G6PD, is crucial for unicellular parasites like Leishmania donovani, making it a key target for drug development.
- Recent studies reveal the unique structure of LdG6PD, highlighting its N-terminal domain and its role in forming a distinct tetramer compared to Trypanosoma G6PDs.
- Insights into LdG6PD's binding mechanism and structural changes during function enhance our understanding of G6PD molecular mechanisms and support future drug discovery efforts.
Article Abstract
Since unicellular parasites highly depend on NADPH as a source for reducing equivalents, the pentose phosphate pathway, especially the first and rate-limiting NADPH-producing enzyme glucose 6-phosphate dehydrogenase (G6PD), is considered an excellent antitrypanosomatid drug target. Here we present the crystal structure of Leishmania donovani G6PD (LdG6PD) elucidating the unique N-terminal domain of Kinetoplastida G6PDs. Our investigations on the function of the N-domain suggest its involvement in the formation of a tetramer that is completely different from related Trypanosoma G6PDs. Structural and functional investigations further provide interesting insights into the binding mode of LdG6PD, following an ordered mechanism, which is confirmed by a G6P-induced domain shift and rotation of the helical N-domain. Taken together, these insights into LdG6PD contribute to the understanding of G6PDs' molecular mechanisms and provide an excellent basis for further drug discovery approaches.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9734377 | PMC |
| http://dx.doi.org/10.1038/s42003-022-04307-7 | DOI Listing |
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