7lj1
Human Prx1-Srx Decameric ComplexHuman Prx1-Srx Decameric Complex
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 PubMedHuman peroxiredoxins (Prx) are a family of antioxidant enzymes involved in a myriad of cellular functions and diseases. During the reaction with peroxides (e.g., H(2)O(2)), the typical 2-Cys Prxs change oligomeric structure between higher order (do)decamers and disulfide-linked dimers, with the hyperoxidized inactive state (-SO(2)H) favoring the multimeric structure of the reduced enzyme. Here, we present a study on the structural requirements for the repair of hyperoxidized 2-Cys Prxs by human sulfiredoxin (Srx) and the relative efficacy of physiological reductants hydrogen sulfide (H(2)S) and glutathione (GSH) in this reaction. The crystal structure of the toroidal Prx1-Srx complex shows an extended active site interface. The loss of this interface within engineered Prx2 and Prx3 dimers yielded variants more resistant to hyperoxidation and repair by Srx. Finally, we reveal for the first time Prx isoform-dependent use of and potential cooperation between GSH and H(2)S in supporting Srx activity. Specificity of Human Sulfiredoxin for Reductant and Peroxiredoxin Oligomeric State.,Forshaw TE, Reisz JA, Nelson KJ, Gumpena R, Lawson JR, Jonsson TJ, Wu H, Clodfelter JE, Johnson LC, Furdui CM, Lowther WT Antioxidants (Basel). 2021 Jun 11;10(6):946. doi: 10.3390/antiox10060946. PMID:34208049[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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