A novel aldo-keto reductase (AKR) was cloned and sequenced from roots of Aloe arborescens by a combination of RT-PCR using degenerate primers based on the conserved sequences of plant polyketide reductases (PKRs) and cDNA library screening by oligonucleotide hybridization. A. arborescens AKR share similarities with known plant AKRs (40-66% amino acid sequence identity), maintaining most of the active-site residues conserved in the AKR superfamily enzymes. Interestingly, despite the sequence similarity with PKRs, recombinant enzyme expressed in Escherichia coli did not exhibit any detectable PKR activities. Instead, A. arborescens AKR catalyzed NADPH-dependent reduction of various carbonyl compounds including benzaldehyde and DL-glyceraldehyde. Finally, a homology model on the basis of the crystal structure of Hordeum vulgare AKR predicted the active-site architecture of the enzyme.
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http://dx.doi.org/10.1248/bpb.30.2262 | DOI Listing |
J Proteome Res
December 2024
Department of Biotechnology, Birla Institute of Technology and Science Pilani (BITS Pilani) - Dubai Campus, Academic City, Dubai, P.O. Box 345055, United Arab Emirates.
Metabolic rewiring is required for cancer cells to survive in harsh microenvironments and is considered to be a hallmark of cancer. Specific metabolic adaptations are required for a tumor to become invasive and metastatic. Cell division and metabolism are inherently interconnected, and several cell cycle modulators directly regulate metabolism.
View Article and Find Full Text PDFFood Chem Toxicol
November 2024
College of Food Science and Engineering, Henan Key Laboratory of Cereal and Oil Food Safety and Nutrition, Henan University of Technology, Zhengzhou, Henan, 450001, China.
Blood Cancer J
November 2024
Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine, UNSW Medicine & Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW, Australia.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that expresses high levels of the enzyme aldo-keto reductase family 1 member C3 (AKR1C3). To exploit this finding, we developed a novel prodrug, ACHM-025, which is selectively activated by AKR1C3 to a nitrogen mustard DNA alkylating agent. We show that ACHM-025 has potent in vivo efficacy against T-ALL patient-derived xenografts (PDXs) and eradicated the disease in 7 PDXs.
View Article and Find Full Text PDFRSC Med Chem
October 2024
Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad Trg Dositeja Obradovića 3 21000 Novi Sad Serbia
In this study, a series of 13 new D-ring fused steroidal (2)-substituted-1,2,3-triazoles were synthesized, characterized and evaluated for their biological activities. The relative binding affinities of the synthesized compounds for the ligand-binding domains of estrogen receptors α and β, androgen receptor and glucocorticoid receptor demonstrated that androstane derivatives 3a and 3h and estratriene derivative 4e showed highly specific and strong binding affinity for estrogen receptor β, while 3b, 3e, 4a and 4b displayed high binding affinity for the glucocorticoid receptor. The synthesized compounds were tested for their ability to inhibit aldo-keto reductases 1C3 and 1C4 by monitoring NADPH consumption using fluorescence spectroscopy.
View Article and Find Full Text PDFBone
January 2025
Department of Orthopaedics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China. Electronic address:
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