Crystal structure of peptide deformylase from <i>Staphylococcus aureus</i> in complex with actinonin, a naturally occurring antibacterial agent

Yoon, Hye‐Jin; Kim, Hye Lee; Lee, Sook-Young; Kim, Hyun Woo; Kim, Hyung-Wook; Lee, Jae Young; Mikami, Bunzo; Suh, Se Won

doi:10.1002/prot.20231

Cited by 21 publications

(24 citation statements)

References 10 publications

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“…6c). Comparison of actinonin-bound HsPDF to a number of representative type 1B, and type 2 PDFs for which an actinonin-bound structure has been elucidated,23,24,32,33 shows a similar conformation for actinonin, except for that in S. aureus . Similarly, most of the hydrogen bond interactions are conserved across PDFs (Supplementary Data Table 1).…”

Section: Resultsmentioning

confidence: 97%

Structure and Activity of Human Mitochondrial Peptide Deformylase, a Novel Cancer Target

Escobar-Alvarez

Goldgur

Yang

et al. 2009

Journal of Molecular Biology

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Peptide deformylase proteins (PDFs) participate in the N-terminal methionine excision pathway of newly synthesized peptides. We show that the human PDF (HsPDF) can deformylate its putative substrates derived from mitochondrial DNA-encoded proteins. The first structural model of a mammalian PDF (1.7 Å), HsPDF, shows a dimer with conserved topology of the catalytic residues and fold as non-mammalian PDFs. The HsPDF C-terminus topology and the presence of a helical loop (H2 and H3), however, shape a characteristic active site entrance. The structure of HsPDF bound to the peptidomimetic inhibitor actinonin (1.7 Å) identified the substrate-binding site. A defined S1′ pocket, but no S2′ or S3′ substrate-binding pockets, exists. A conservation of PDF–actinonin interaction across PDFs was observed. Despite the lack of true S2′ and S3′ binding pockets, confirmed through peptide binding modeling, enzyme kinetics suggest a combined contribution from P2′ and P3′ positions of a formylated peptide substrate to turnover.

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Section: Resultsmentioning

confidence: 97%

Structure and Activity of Human Mitochondrial Peptide Deformylase, a Novel Cancer Target

Escobar-Alvarez

Goldgur

Yang

et al. 2009

Journal of Molecular Biology

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“…According to the representation shown in Figure 2B, Plasmodium falciparum PDF ( Pf PDF), a poorly active PDF [61], was retrieved only in the S state. Finally, weak decompaction of the structure of Bacillus cereus and Staphylococcus aureus PDFs in the presence of actinonin have been described [45],[46]. These examples suggest that the enzyme is trapped in the S conformer in the free state and converts to the C conformer when bound to actinonin, suggesting that the S conformer is overrepresented in solution compared to the O state, unlike At PDF.…”

Section: Discussionmentioning

confidence: 99%

Trapping Conformational States Along Ligand-Binding Dynamics of Peptide Deformylase: The Impact of Induced Fit on Enzyme Catalysis

et al. 2011

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For several decades, molecular recognition has been considered one of the most fundamental processes in biochemistry. For enzymes, substrate binding is often coupled to conformational changes that alter the local environment of the active site to align the reactive groups for efficient catalysis and to reach the transition state. Adaptive substrate recognition is a well-known concept; however, it has been poorly characterized at a structural level because of its dynamic nature. Here, we provide a detailed mechanism for an induced-fit process at atomic resolution. We take advantage of a slow, tight binding inhibitor-enzyme system, actinonin-peptide deformylase. Crystal structures of the initial open state and final closed state were solved, as well as those of several intermediate mimics captured during the process. Ligand-induced reshaping of a hydrophobic pocket drives closure of the active site, which is finally “zipped up” by additional binding interactions. Together with biochemical analyses, these data allow a coherent reconstruction of the sequence of events leading from the encounter complex to the key-lock binding state of the enzyme. A “movie” that reconstructs this entire process can be further extrapolated to catalysis.

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“…The metalloproteinase PDF has a very important role in bacteria in removing the N -formyl group from the terminal methionine residue of nascent proteins, a necessary step to complete protein biosynthesis and maturation. The crystal structure of S. aureus PDF has been studied in complex with the naturally occurring antibacterial agent actinonin, and it has revealed its high potential to be used as a specific target for the discovery of broad spectrum antibacterial drugs (Yoon et al, 2004). The nitroreductase enzyme in spot#4 corresponded to the studied NfrA protein of S. aureus (Streker et al, 2005), which was found capable of reducing FMN in the presence of NADPH, reducing organic nitro compounds like nitrofurantoin and nitrofurazone, and exhibiting weak disulfide reductase activity.…”

Section: Resultsmentioning

confidence: 99%

Effect of Rocket (Eruca sativa) Extract on MRSA Growth and Proteome: Metabolic Adjustments in Plant-Based Media

et al. 2017

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The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in food has provoked a great concern about the presence of MRSA in associated foodstuff. Although MRSA is often detected in various retailed meat products, it seems that food handlers are more strongly associated with this type of food contamination. Thus, it can be easily postulated that any food could be contaminated with this pathogen in an industrial environment or in household and cause food poisoning. To this direction, the effect of rocket (Eruca sativa) extract on MRSA growth and proteome was examined in the present study. This goal was achieved with the comparative study of the MRSA strain COL proteome, cultivated in rocket extract versus the standard Luria-Bertani growth medium. The obtained results showed that MRSA was able to grow in rocket extract. In addition, proteome analysis using 2-DE method showed that MRSA strain COL is taking advantage of the sugar-, lipid-, and vitamin-rich substrate in the liquid rocket extract, although its growth was delayed in rocket extract compared to Luria–Bertani medium. This work could initiate further research about bacterial metabolism in plant-based media and defense mechanisms against plant-derived antibacterials.

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Crystal structure of peptide deformylase from Staphylococcus aureus in complex with actinonin, a naturally occurring antibacterial agent

Cited by 21 publications

References 10 publications

Structure and Activity of Human Mitochondrial Peptide Deformylase, a Novel Cancer Target

Structure and Activity of Human Mitochondrial Peptide Deformylase, a Novel Cancer Target

Trapping Conformational States Along Ligand-Binding Dynamics of Peptide Deformylase: The Impact of Induced Fit on Enzyme Catalysis

Effect of Rocket (Eruca sativa) Extract on MRSA Growth and Proteome: Metabolic Adjustments in Plant-Based Media

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