9lg0
From Proteopedia
Crystal Structure of Human Peroxiredoxin I in Complex with SAB
Structural highlights
FunctionPRDX1_HUMAN Involved in redox regulation of the cell. Reduces peroxides with reducing equivalents provided through the thioredoxin system but not from glutaredoxin. May play an important role in eliminating peroxides generated during metabolism. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2). Reduces an intramolecular disulfide bond in GDPD5 that gates the ability to GDPD5 to drive postmitotic motor neuron differentiation (By similarity). Publication Abstract from PubMedRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases. Augmentation of PRDX1-DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation.,Dang W, Wang X, Li H, Xu Y, Li X, Huang S, Tao H, Li X, Yang Y, Xuan L, Xiao W, Guo D, Zhang H, Wu Q, Zheng J, Shen X, Chen K, Xu H, Zhang Y, Luo C Acta Pharm Sin B. 2025 Aug;15(8):3997-4013. doi: 10.1016/j.apsb.2025.06.006. Epub , 2025 Jun 9. PMID:40893682[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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