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http://dx.doi.org/10.1016/j.apsb.2024.06.025 | DOI Listing |
Nucleic Acids Res
January 2025
Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Sector 81, Knowledge City, SAS Nagar, Mohali 140306, Punjab, India.
GntR/FadR family featuring an N-terminal winged helix-turn-helix DNA-binding domain and a C-terminal α-helical effector-binding and oligomerization domain constitutes one of the largest families of transcriptional regulators. Several GntR/FadR regulators govern the metabolism of sugar acids, carbon sources implicated in bacterial-host interactions. Although effectors are known for a few sugar acid regulators, the unavailability of relevant structures has left their allosteric mechanism unexplored.
View Article and Find Full Text PDFBlood Adv
January 2025
KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
Allosteric regulation of ADAMTS13 (A Disintegrin And Metalloproteinase with ThromboSpondin type-1 motif, member 13) activity involves an interaction between its Spacer (S) and CUB1-2 domains to keep the enzyme in a closed, latent conformation. Monoclonal antibodies (mAb) uncouple the S-CUB interaction to open the ADAMTS13 conformation and thereby disrupt the global enzyme latency. The molecular mechanism behind this mAb-induced allostery remains poorly understood.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Applied Biological Science, Tokyo University of Agriculture and Technology, Fuchu 183-8509, Japan.
Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with epoxide hydrolase activity in the C-terminal domain (C-EH) and lipid phosphate phosphatase activity in the N-terminal domain (N-phos). The C-EH hydrolyzes bioactive epoxy fatty acids such as epoxyeicosatrienoic acid (EET). The N-phos hydrolyzes lipid phosphomonesters, including the signaling molecules of lysophosphatidic acid (LPA).
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Biliverdin reductase B (BLVRB) is a redox regulator that catalyzes nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductions of multiple substrates, including flavins and biliverdin-β. BLVRB has emerging roles in redox regulation and post-translational modifications, highlighting its importance in various physiological contexts. In this study, we explore the structural and functional differences between human BLVRB and its hyrax homologue, focusing on evolutionary adaptations at the active site and allosteric regions.
View Article and Find Full Text PDFCells
December 2024
Centre for Health and Life Sciences, Coventry University, Coventry CV1 5FB, UK.
The adenosine A1 receptor (AR) is a promising target for pain treatment. However, the development of therapeutic agonists is hampered by adverse effects, mainly including sedation, bradycardia, hypotension, or respiratory depression. Recently discovered molecules able to overcome this impediment are the positive allosteric modulator MIPS521 and the A1R-selective agonist BnOCPA, which are both potent and powerful analgesics with fewer side effects.
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