5b8a
Crystal structure of oxidized chimeric EcAhpC1-186-YFSKHNCrystal structure of oxidized chimeric EcAhpC1-186-YFSKHN
Structural highlights
FunctionAHPC_ECOLI Directly reduces organic hydroperoxides in its reduced dithiol form.PRDX2_HUMAN Involved in redox regulation of the cell. Reduces peroxides with reducing equivalents provided through the thioredoxin system. It is not able to receive electrons 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). Publication Abstract from PubMedIn addition to their antioxidant function, the eukaryotic peroxiredoxins (Prxs) facilitate peroxide-mediated signaling by undergoing controlled inactivation by peroxide-driven over-oxidation. In general, the bacterial enzyme lacks this controlled inactivation mechanism, making it more resistant to high H2O2 concentrations. During peroxide reduction, the active site alternates between reduced, fully folded (FF), and oxidized, locally unfolded (LU) conformations. Here we present novel insights into the divergence of bacterial and human Prxs in robustness and sensitivity to inactivation, respectively. Structural details provide new insights into sub-steps during the catalysis of peroxide reduction, enabling the transition from an FF to a LU conformation. Complementary to mutational and enzymatic results, these data unravel the essential role of the C-terminal tail of bacterial Prxs to act as a molecular switch, mediating the transition from an FF to a LU state. In addition, we propose that the C-terminal tail has influence on the propensity of the disulphide bond formation, indicating that as a consequence on the robustness and sensitivity to over-oxidation. Finally, a physical linkage between the catalytic site, the C-terminal tail and the oligomer interface is described. Transition steps in peroxide reduction and a molecular switch for peroxide robustness of prokaryotic peroxiredoxins.,Kamariah N, Sek MF, Eisenhaber B, Eisenhaber F, Gruber G Sci Rep. 2016 Nov 28;6:37610. doi: 10.1038/srep37610. PMID:27892488[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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