3hy2
From Proteopedia
Crystal Structure of Sulfiredoxin in Complex with Peroxiredoxin I and ATP:Mg2+
Structural highlights
Function[PRDX1_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). [SRXN1_HUMAN] Contributes to oxidative stress resistance by reducing cysteine-sulfinic acid formed under exposure to oxidants in the peroxiredoxins PRDX1, PRDX2, PRDX3 and PRDX4. Does not act on PRDX5 or PRDX6. May catalyze the reduction in a multi-step process by acting both as a specific phosphotransferase and a thioltransferase.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedOxidative stress can damage the active site cysteine of the antioxidant enzyme peroxiredoxin (Prx) to the sulfinic acid form, Prx-SO(2)(-). This modification leads to inactivation. Sulfiredoxin (Srx) utilizes a unique ATP-Mg(2+)-dependent mechanism to repair the Prx molecule. Using selective protein engineering that involves disulfide bond formation and site-directed mutagenesis, a mimic of the enzyme.substrate complex has been trapped. Here, we present the 2.1 A crystal structure of human Srx in complex with PrxI, ATP, and Mg(2+). The Cys(52) sulfinic acid moiety was substituted by mutating this residue to Asp, leading to a replacement of the sulfur atom with a carbon atom. Because the Srx reaction cannot occur, the structural changes in the Prx active site that lead to the attack on ATP may be visualized. The local unfolding of the helix containing C52D resulted in the packing of Phe(50) in PrxI within a hydrophobic pocket of Srx. Importantly, this structural rearrangement positioned one of the oxygen atoms of Asp(52) within 4.3 A of the gamma-phosphate of ATP bound to Srx. These observations support a mechanism where phosphorylation of Prx-SO(2)(-) is the first chemical step. Protein engineering of the quaternary sulfiredoxin.peroxiredoxin enzyme.substrate complex reveals the molecular basis for cysteine sulfinic acid phosphorylation.,Jonsson TJ, Johnson LC, Lowther WT J Biol Chem. 2009 Nov 27;284(48):33305-10. Epub 2009 Oct 6. PMID:19812042[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Peroxiredoxin | Johnson, L C | Jonsson, T J | Lowther, W T | Antioxidant | Atp-binding | Disulfide bond | Magnesium | Nucleotide-binding | Oxidoreductase | Peroxidase | Phosphoprotein | Protein repair | Protein-protein complex | Redox biology | Redox-active center | Sulfur chemistry
