The Thioredoxin Domain of Neisseria gonorrhoeae PilB Can Use Electrons from DsbD to Reduce Downstream Methionine Sulfoxide Reductases

Brot, Nathan; Collet, Jean-François; Johnson, Lynnette C.; Jönsson, Thomas J.; Weissbach, Herbert; Lowther, W. Todd

doi:10.1074/jbc.m604971200

Cited by 37 publications

(41 citation statements)

References 42 publications

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“…uid ϭ cd02966); thus, we named this protein TlpA. Proteins belonging to this family have been shown to play an important role in the response against oxidative stress (7,9,19,32). Interestingly, the ORF was identified in two previous signature-tagged mutagenesis (STM) studies as being required for successful animal passage (10,28).…”

Section: Resultsmentioning

confidence: 99%

Pneumococcal Gene Complex Involved in Resistance to Extracellular Oxidative Stress

et al. 2012

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Streptococcus pneumoniae is a Gram-positive bacterium which is a member of the normal human nasopharyngeal flora but can also cause serious disease such as pneumonia, bacteremia, and meningitis. Throughout its life cycle, S. pneumoniae is exposed to significant oxidative stress derived from endogenously produced hydrogen peroxide (H 2 O 2 ) and from the host through the oxidative burst. How S. pneumoniae, an aerotolerant anaerobic bacterium that lacks catalase, protects itself against hydrogen peroxide stress is still unclear. Bioinformatic analysis of its genome identified a hypothetical open reading frame belonging to the thiol-specific antioxidant (TlpA/TSA) family, located in an operon consisting of three open reading frames. For all four strains tested, deletion of the gene resulted in an approximately 10-fold reduction in survival when strains were exposed to external peroxide stress. However, no role for this gene in survival of internal superoxide stress was observed. Mutagenesis and complementation analysis demonstrated that all three genes are necessary and sufficient for protection against oxidative stress. Interestingly, in a competitive index mouse pneumonia model, deletion of the operon had no impact shortly after infection but was detrimental during the later stages of disease. Thus, we have identified a gene complex involved in the protection of S. pneumoniae against external oxidative stress, which plays an important role during invasive disease.

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Section: Resultsmentioning

confidence: 99%

Pneumococcal Gene Complex Involved in Resistance to Extracellular Oxidative Stress

et al. 2012

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“…As an electron donor is needed to maintain the catalytic activity of methionine sulfoxide reductase [83], it can be hypothesized that the DsbD-family proteins transfer electrons across the membrane and the thioredoxin-like lipoprotein relays the electrons to reduce the secreted methionine sulfoxide reductase. This pathway for electron transfer has received experimental support from elegant studies of the periplasmic PilB methionine sulfoxide reductase of Neisseria gonorrhoeae, which has a fused thioredoxin lipoprotein domain at its N-terminus and is likewise maintained by a cognate DsbD family protein [84]. Cumulatively, these examples illustrate that lipoproteins are appropriately localized to participate in cytoplasmic membrane redox processes.…”

Section: Reviewmentioning

confidence: 97%

Lipoprotein biogenesis in Gram-positive bacteria: knowing when to hold ‘em, knowing when to fold ‘em

Hutchings

Palmer

Harrington

et al. 2009

Trends in Microbiology

181

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“…Coupling MsrAB to a thioredoxin domain (i.e., NT) at the N-terminus of MsrAB in Neisseria efficiently reduces the active site in both catalytic domains in the absence of added thioredoxin (22). Cytosolic reducing potential (i.e., NADPH) is coupled to the MsrAB systems through the integral membrane protein DspD, which promotes the reduction of the active sites in both MsrA and MsrB domains of MsrAB (22). These results suggested that enzyme fusion in bifunctional Msr enzymes functions primarily as an organizing mechanism to effectively couple the cytosolic reducing equivalents to active MsrA and MsrB sites in the periplasm.…”

Section: Discussionmentioning

confidence: 99%

“…Bifunctional Msr enzymes, which reduce both S-and R-diastereomers of MetSO, are present in many pathogenic and metal-reducing bacteria (including Haemophilus influenze, Helicobacter pylori, Vibrio cholerae, Neisseria meningitidis, Bacillus anthracis, and Shewanella oneidensis), and have arisen through gene fusion to create both MsrAB or MsrBA variants (8). These fusion proteins are commonly located on the outer surface of the inner membrane in the periplasm, permitting the efficient redox coupling of cytosolic NADPH to maintain these enzymes in a reduced state necessary for the repair of oxidized proteins (11,22). It remains unclear whether the formation of bifunctional Msr enzymes through gene fusion has any additional functional significance that may, for example, be related to the catalytic ability to simultaneously bind multiple MetSO within an oxidized protein.…”

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confidence: 99%

Increased Catalytic Efficiency following Gene Fusion of Bifunctional Methionine Sulfoxide Reductase Enzymes from Shewanella oneidensis

et al. 2007

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Methionine sulfoxide reductase enzymes MsrA and MsrB have complementary stereospecificies that respectively reduce the S-and R-stereoisomers of methionine sulfoxide (MetSO), and together function as critical antioxidant enzymes. In some pathogenic and metal -reducing bacteria these genes are fused to form a bifunctional methionine sulfoxide reductase (i.e., MsrBA) enzyme. To investigate how gene fusion affects the substrate specificity and catalytic activities of Msr, we have cloned and expressed the MsrBA enzyme from Shewanella oneidensis, a metal-reducing bacterium and fish pathogen. For comparison, we also cloned and expressed the wild-type MsrA enzyme from Shewanella oneidensis and a genetically engineered MsrB protein. MsrBA is able to completely reduce (i.e., repair) MetSO in the calcium regulatory protein calmodulin (CaM); while only partial repair is observed using both MsrA and MsrB enzymes together at 25 °C. A restoration of the normal protein fold is observed coincident with the repair of MetSO in oxidized CaM by MsrBA, as monitored by the time-dependent increases in the anisotropy associated with the rigidly bound multiuse affinity probe 4′5′-bis(1,3,2-dithoarsolan-2yl)fluorescein (FlAsH). Underlying the efficient repair of MetSO in oxidized CaM is the coordinate activity of the two catalytic domains in the MsrBA fusion protein, which results in an order of magnitude rate enhancement in comparison to the individual MsrA or MsrB enzymes alone. The coordinate binding of both domains of MsrBA permits the full repair of all MetSO in CaM ox . The common expression of Msr fusion proteins in bacterial pathogens is consistent with an important role for this enzyme activity in the maintenance of protein function necessary for bacterial survival under highly oxidizing conditions associated with pathogenesis or bioremediation.Methionines are highly susceptible to oxidation to their corresponding methionine sulfoxides (MetSO 1 ) by a range of commonly generated reactive oxygen species (ROS), such as hydrogen peroxide, singlet oxygen, or peroxynitrite (1-3). Methionine sulfoxide reductase (Msr) enzymes recognize MetSO within unfolded sequences of proteins, and bind with high-affinity (i.e., K d = 70 ± 10 nM) prior to the reduction of MetSO to restore the native Met structure (4-6). In addition, distinct Msr enzymes are critical to the maintenance of cellular Met pools (7), whose oxidation can down-regulate the initiation of protein synthesis.Two different enzyme classes of Msr, i.e., MsrA and MsrB, are expressed in virtually all organisms (8,9). While these enzymes have little structural homology, the catalytic sites of MsrA and MsrB possess a mirror image symmetry that promotes the selective reduction of Sand R-diastereomers of . High-affinity binding and reduction of free MetSO

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The Thioredoxin Domain of Neisseria gonorrhoeae PilB Can Use Electrons from DsbD to Reduce Downstream Methionine Sulfoxide Reductases

Cited by 37 publications

References 42 publications

Pneumococcal Gene Complex Involved in Resistance to Extracellular Oxidative Stress

Pneumococcal Gene Complex Involved in Resistance to Extracellular Oxidative Stress

Lipoprotein biogenesis in Gram-positive bacteria: knowing when to hold ‘em, knowing when to fold ‘em

Increased Catalytic Efficiency following Gene Fusion of Bifunctional Methionine Sulfoxide Reductase Enzymes from Shewanella oneidensis

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