| 1. |
- Zhang, R. Y., et al.
(författare)
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Lysozyme's lectin-like characteristics facilitates its immune defense function
- 2017
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Ingår i: Quarterly Reviews of Biophysics. - : Cambridge University Press (CUP). - 0033-5835 .- 1469-8994. ; 50, s. 1-12
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Forskningsöversikt (refereegranskat)abstract
- Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.
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| 2. |
- Zhang, R. Y., et al.
(författare)
-
Lysozyme's lectin-like characteristics facilitates its immune defense function
- 2017
-
Ingår i: Quarterly Reviews of Biophysics. - : Cambridge University Press (CUP). - 1469-8994 .- 0033-5835. ; 50, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.
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| 3. |
- Datta, A., et al.
(författare)
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Role of Aromatic Amino Acids in Lipopolysaccharide and Membrane Interactions of Antimicrobial Peptides for use in Plant Disease Control
- 2016
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 291:25, s. 13301-13317
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Tidskriftsartikel (refereegranskat)abstract
- KYE28(KYEITTIHNLFRKLTHRLFRRNFGYTLR), the representative sequence of helix D of heparin co-factor II, was demonstrated to be potent against agronomically important Gram-negative plant pathogens X. vesicatoria and X. oryzae,capable of inhibiting disease symptoms in detached tomato leaves. NMR studies in presence of lipopolysaccharide provided structural insights into the mechanisms underlying this, notably in relation to outer membrane permeabilisation. The three-dimensional solution structure of KYE28 in LPS is characterised by a N-ter helical segment, an intermediate loop and an extended C-ter. The two termini are in close proximity to each other via aromatic packing interactions, while the positively charged residues formed an exterior polar shell. To further demonstrate the importance of the aromatic residues for this, a mutant peptide KYE28A, with Ala substitutions at F11, F19, F23 and Y25 showed attenuated antimicrobial activity at high salt concentrations, as well as lower membrane disruption and LPS binding abilities compared to KYE28. In contrast to KYE28, KYE28A adopted an opened out helical structure in LPS with extended N- and C-ter and a small break in between the helical segments. Aromatic packing interactions were completely lost, although hydrophobic interaction between the side chains of hydrophobic residues were still partly retained, imparting an amphipathic character and explaining its residual antimicrobial activity and LPS binding as observed from ellipsometry and ITC. We thus present important structural aspects of KYE28, constituting an aromatic zipper, of potential importance, for the development of novel plant protection agents and therapeutic agents.
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| 4. |
- Bhunia, Asamanjoy, et al.
(författare)
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Formal water oxidation turnover frequencies from MIL-101(Cr) anchored Ru(bda) depend on oxidant concentration
- 2018
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Ingår i: Chemical Communications. - : ROYAL SOC CHEMISTRY. - 1359-7345 .- 1364-548X. ; 54, s. 7770-7773
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Tidskriftsartikel (refereegranskat)abstract
- The molecular water oxidation catalyst [Ru(bda)(L)(2)] has been incorporated into pyridine-decorated MIL-101(Cr) metal-organic frameworks. The resulting MIL-101@Ru materials exhibit turnover frequencies (TOFs) up to ten times higher compared to the homogenous reference. An unusual dependence of the formal TOFs on oxidant concentration is observed that ultimately arises from differing amounts of catalysts in the MOF crystals being active.
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| 5. |
- Ilyas, Humaira, et al.
(författare)
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Effect of PEGylation on Host Defense Peptide Complexation with Bacterial Lipopolysaccharide
- 2021
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Ingår i: Bioconjugate Chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 32:8, s. 1729-1741
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Tidskriftsartikel (refereegranskat)abstract
- Conjugation with poly(ethylene glycol) ("PEGylation") is a widely used approach for improving the therapeutic propensities of peptide and protein drugs through prolonging bloodstream circulation, reducing toxicity and immunogenicity, and improving proteolytic stability. In the present study, we investigate how PEGylation affects the interaction of host defense peptides (HDPs) with bacterial lipopolysaccharide (LPS) as well as HDP suppression of LPS-induced cell activation. In particular, we investigate the effects of PEGylation site for KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR), a peptide displaying potent anti-inflammatory effects, primarily provided by its N-terminal part. PEGylation was performed either in the N-terminus, the C-terminus, or in both termini, keeping the total number of ethylene groups (n = 48) constant. Ellipsometry showed KYE28 to exhibit pronounced affinity to both LPS and its hydrophobic lipid A moiety. The PEGylated peptide variants displayed lower, but comparable, affinity for both LPS and lipid A, irrespective of the PEGylation site. Furthermore, both KYE28 and its PEGylated variants triggered LPS aggregate disruption. To investigate the peptide structure in such LPS complexes, a battery of nuclear magnetic resonance (NMR) methods was employed. From this, it was found that KYE28 formed a well-folded structure after LPS binding, stabilized by hydrophobic domains involving aromatic amino acids as well as by electrostatic interactions. In contrast, the PEGylated peptide variants displayed a less well-defined secondary structure, suggesting weaker LPS interactions in line with the ellipsometry findings. Nevertheless, the N-terminal part of KYE28 retained helix formation after PEGylation, irrespective of the conjugation site. For THP1-Xblue-CD14 reporter cells, KYE28 displayed potent suppression of LPS activation at simultaneously low cell toxicity. Interestingly, the PEGylated KYE28 variants displayed similar or improved suppression of LPS-induced cell activation, implying the underlying key role of the largely retained helical structure close to the N-terminus, irrespective of PEGylation site. Taken together, the results show that PEGylation of HDPs can be done insensitively to the conjugation site without losing anti-inflammatory effects, even for peptides inducing such effects through one of its termini.
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| 6. |
- Johnson, Ben A., et al.
(författare)
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Development of a UiO-Type Thin Film Electrocatalysis Platform with Redox-Active Linkers
- 2018
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 140:8, s. 2985-2994
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Tidskriftsartikel (refereegranskat)abstract
- Metal–organic frameworks (MOFs) as electrocatalysis scaffolds are appealing due to the large concentration of catalytic units that can be assembled in three dimensions. To harness the full potential of these materials, charge transport to the redox catalysts within the MOF has to be ensured. Herein, we report the first electroactive MOF with the UiO/PIZOF topology (Zr(dcphOH-NDI)), i.e., one of the most widely used MOFs for catalyst incorporation, by using redox-active naphthalene diimide-based linkers (dcphOH-NDI). Hydroxyl groups were included on the dcphOH-NDI linker to facilitate proton transport through the material. Potentiometric titrations of Zr(dcphOH-NDI) show the proton-responsive behavior via the −OH groups on the linkers and the bridging Zr-μ3-OH of the secondary building units with pKa values of 6.10 and 3.45, respectively. When grown directly onto transparent conductive fluorine-doped tin oxide (FTO), 1 μm thin films of Zr(dcphOH-NDI)@FTO could be achieved. Zr(dcphOH-NDI)@FTO displays reversible electrochromic behavior as a result of the sequential one-electron reductions of the redox-active NDI linkers. Importantly, 97% of the NDI sites are electrochemically active at applied potentials. Charge propagation through the thin film proceeds through a linker-to-linker hopping mechanism that is charge-balanced by electrolyte transport, giving rise to cyclic voltammograms of the thin films that show characteristics of a diffusion-controlled process. The equivalent diffusion coefficient, De, that contains contributions from both phenomena was measured directly by UV/vis spectroelectrochemistry. Using KPF6 as electrolyte, De was determined to be De(KPF6) = (5.4 ± 1.1) × 10–11 cm2 s–1, while an increase in countercation size to n-Bu4N+ led to a significant decrease of De by about 1 order of magnitude (De(n-Bu4NPF6) = (4.0 ± 2.5) × 10–12 cm2 s–1).
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| 7. |
- Johnson, Ben A., et al.
(författare)
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Electrocatalytic water oxidation by a molecular catalyst incorporated into a metal-organic framework thin film
- 2017
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Ingår i: Dalton Transactions. - : ROYAL SOC CHEMISTRY. - 1477-9226 .- 1477-9234. ; 46:5, s. 1382-1388
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Tidskriftsartikel (refereegranskat)abstract
- A molecular water oxidation catalyst, [Ru(tpy)(dcbpy)(OH2)](ClO4)(2) (tpy = 2,2': 6',2''-terpyridine, dcbpy = 2,2'-bipyridine- 5,5'-dicarboxylic acid) [1], has been incorporated into FTO-grown thin films of UiO-67 (UiO = University of Oslo), by post-synthetic ligand exchange. Cyclic voltammograms (0.1 M borate buffer at pH = 8.4) of the resulting UiO67-[RuOH2]@ FTO show a reversible wave associated with the Ru-III/II couple in the anodic scan, followed by a large current response that arises from electrocatalytic water oxidation beyond 1.1 V vs. Ag/AgCl. Water oxidation can be observed at an applied potential of 1.5 V over the timescale of hours with a current density of 11.5 mu A cm(-2). Oxygen evolution was quantified in situ over the course of the experiment, and the Faradaic efficiency was calculated as 82%. Importantly, the molecular integrity of [1] during electrocatalytic water oxidation is maintained even on the timescale of hours under turnover conditions and applied voltage, as evidenced by the persistence of the wave associated with the Ru-III/II couple in the CV. This experiment highlights the capability of metal organic frameworks like UiO-67 to stabilize the molecular structure of catalysts that are prone to form higher clusters in homogenous phase.
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