Dehydrogenases are oxidoreductase enzymes that play a variety of fundamental functions in the living organisms and have primary roles in pathogen survival and infection processes as well as in cancer development. We review here a sub-set of NAD-dependent dehydrogenases involved in human diseases and the recent advancements in drug development targeting pathogen-associated NAD-dependent dehydrogenases. We focus also on the molecular aspects of the inhibition process listing the structures of the most relevant molecules targeting this enzyme family. Our aim is to review the most impacting findings regarding the discovery of novel inhibitory compounds targeting the selected NAD-dependent dehydrogenases involved in cancer and infectious diseases.
The cover shows a metaphorical representation of the anti-CRISPR AcrIIA6, represented as handcuffs, sequestering two Streptococcus thermophilus CRISPR1-Cas9 (St1Cas9) molecules at a time and preventing conformational changes associated with DNA recognition and binding. In the absence of AcrIIA6, St1Cas9 tightly binds to its target DNA, and can proceed to target cleavage. For further information, see the article by Hardouin and Goulet in this issue (pp. 507–516). This cover artwork has been made by Beata Edyta Mierzwa (www.BeataScienceArt.com).
Targeting NAD-dependent dehydrogenases in drug discovery against infectious diseases and cancer
Davide M. Ferraris, Edoardo L. M. Gelardi, Silvia Garavaglia, Riccardo Miggiano, Menico Rizzi; Targeting NAD-dependent dehydrogenases in drug discovery against infectious diseases and cancer. Biochem Soc Trans 29 April 2020; 48 (2): 693–707. doi: https://doi.org/10.1042/BST20191261
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