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Publication Abstract from PubMed

Members of the human aldehyde dehydrogenase family 1 (ALDH1As) play a crucial role in converting retinal to retinoic acid, a multifunctional bioactive compound. Most evidence highlight ALDH1As as markers for cancer stem cells correlating with tumour aggressiveness. Increasing structural and biochemical data about these important isoenzymes have been reported in literature. Crystal structures of human ALDH1A2 have been so far only obtained in the presence of ligands/cofactors from vapour diffusion hanging drops. Apo-enzyme structures have been described only for the other two members of the family (ALDH1A1 and ALDH1A3) serving as the basis for their co-crystallisation with various ligands. In this study, we describe the first apo-ALDH1A2 structure obtained from nanolitre sitting-drop crystallisation, which expands the potential for high-throughput structure-based drug discovery studies on this isoform. We also explore the crystallisability of NAD(+)-ALDH1A3 from microlitre drops and compare the structure obtained from it with that of apo-ALDH1A2. Finally, we propose strategies compatible with robotic setups to streamline structural studies on ALDH1A3 and facilitate the exploration of extensive ligand libraries.

Exploiting ALDH1A2 and ALDH1A3 isoform variability for crystallisation screening.,Siragusa S, Garavaglia S, Mazzorana M Biochem Biophys Res Commun. 2025 Aug 14;780:152469. doi: , 10.1016/j.bbrc.2025.152469. PMID:40829477^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.