5fa9 | pdb_00005fa9
Bifunctional Methionine Sulfoxide Reductase AB (MsrAB) from Treponema denticola
Structural highlights
FunctionQ73PT7_TREDE Has an important function as a repair enzyme for proteins that have been inactivated by oxidation. Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine.[HAMAP-Rule:MF_01401] Publication Abstract from PubMedMany bacteria, particularly pathogens, possess methionine sulfoxide reductase A (MsrA) and B (MsrB) as a fusion form (MsrAB). However, it is not clear why they possess a fusion MsrAB form rather than the separate enzymes that exist in most organisms. In this study, we performed biochemical and kinetic analyses of MsrAB from Treponema denticola (TdMsrAB), single-domain forms (TdMsrA and TdMsrB), and catalytic Cys mutants (TdMsrAB(C11S) and TdMsrAB(C285S)). We found that the catalytic efficiency of both MsrA and MsrB increased after fusion of the domains and that the linker region (iloop) that connects TdMsrA and TdMsrB is required for the higher catalytic efficiency of TdMsrAB. We also determined the crystal structure of TdMsrAB at 2.3 A, showing that the iloop mainly interacts with TdMsrB via hydrogen bonds. Further kinetic analysis using the iloop mutants revealed that the iloop-TdMsrB interactions are critical to MsrB and MsrA activities. We also report the structure in which an oxidized form of dithiothreitol, an in vitro reductant for MsrA and MsrB, is present in the active site of TdMsrA. Collectively, the results of this study reveal an essential role of the iloop in maintaining the higher catalytic efficiency of the MsrAB fusion enzyme and provide a better understanding of why the MsrAB enzyme exists as a fused form. Essential Role of the Linker Region in the Higher Catalytic Efficiency of a Bifunctional MsrA-MsrB Fusion Protein.,Han AR, Kim MJ, Kwak GH, Son J, Hwang KY, Kim HY Biochemistry. 2016 Sep 13;55(36):5117-27. doi: 10.1021/acs.biochem.6b00544. Epub , 2016 Sep 1. PMID:27551953[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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