Cholesterol is a ubiquitous component of eukaryotic cell membranes and a key molecule in controll... more Cholesterol is a ubiquitous component of eukaryotic cell membranes and a key molecule in controlling membrane fluidity, packing state, and various biological processes. It also plays a regulatory function in the immune response and antibiotic drug resistance by augmenting the membrane mechanical properties against structural damage. While it is well understood that, structurally, cholesterol exhibits a universal condensing effect on lipid membranes, its effects on membrane mechanics are assumed to be non-universal; i.e. cholesterol causes noticeable stiffening in saturated lipid membranes, but is surprisingly reported to have no stiffening effect on unsaturated lipid membranes such as DOPC. Here, using neutron spin-echo (NSE) spectroscopy, solid-state deuterium nuclear magnetic resonance (2H-NMR) spectroscopy, and molecular dynamics (MD) simulations, we report that, on the mesoscale, cholesterol increases the bending rigidity of DOPC membranes, similar to saturated membranes, throug...
CW saturation experiments are widely used in ESR studies of relaxation processes in proteins and ... more CW saturation experiments are widely used in ESR studies of relaxation processes in proteins and lipids. We develop the theory of saturation in ESR spectra in terms of its close relation with that of 2D-ELDOR. Our treatment of saturation is then based on the microscopic order macroscopic disorder (MOMD) model and can be used to fit the full CW saturation spectrum, rather than fitting just the peak–peak amplitude as a function of microwave field $$B_1$$ B 1 as is commonly done. This requires fewer experiments to yield effects on $$T_1$$ T 1 , as well as provides a more extensive dynamic structural picture, for example, for scanning experiments on different protein sites. The code is released as a publicly available software package in Python that can be used to fit CW saturation spectra from biological samples of interest.
Proceedings of the National Academy of Sciences, 2020
Significance Cholesterol regulates critical cell functions, including lysis, viral budding, and a... more Significance Cholesterol regulates critical cell functions, including lysis, viral budding, and antibiotic resistance, by modifying the bending rigidity of cell membranes; i.e., the ability of membranes to bend or withstand mechanical stresses. A molecular-level understanding of these functions requires knowledge of how cholesterol modifies membrane mechanics over relevant length and time scales. Currently, it is widely accepted that cholesterol has no effect on the mechanical properties of unsaturated lipid membranes, implying that viruses, for example, can bud from regions enriched in (poly)unsaturated lipids. Our observations that cholesterol causes local stiffening in DOPC membranes indicate that a reassessment of existing concepts is necessary. These findings have far-reaching implications in understanding cholesterol’s role in biology and its applications in bioengineering and drug design.
Transition metal ion doped one-dimensional (1-D) nanocrystals (NCs) have advantages of larger abs... more Transition metal ion doped one-dimensional (1-D) nanocrystals (NCs) have advantages of larger absorption cross sections and polarized absorption and emissions in comparison to 0-D NCs. However, direct synthesis of doped 1-D nanorods (NRs) or nanowires (NWs) has proven challenging. In this study, we report the synthesis of 1-D Mn-doped ZnSe NWs using a colloidal hot-injection method and shell passivation for core/shell NWs with tunable optical properties. Experimental results show optical properties of the NWs are controlled by the composition and thickness of the shell lattice. It was found that both the host-Mn energy transfer and Mn-Mn coupling are strongly dependent on the type of alloy at the interface of doped core/shell NWs. For Mn-doped type I ZnSe/ZnS core/shell NWs, the ZnS shell passivation can enhance florescence quantum yield with little effect on the location of the incorporated Mn dopant due to the identical cationic Zn site available for Mn dopants throughout the core...
Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed by a radical S-... more Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed by a radical S-adenosylmethionine (SAM) enzyme that cleaves a carbon-sulfur (C-S) bond in SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. Using rapid freezing, we have captured an organometallic intermediate with an iron-carbon (Fe-C) bond between ACP and the enzyme's [4Fe-4S] cluster. In the presence of the substrate protein, elongation factor 2, this intermediate converts to an organic radical, formed by addition of the ACP radical to a histidine side chain. Crystal structures of archaeal diphthamide biosynthetic radical SAM enzymes reveal that the carbon of the SAM C-S bond being cleaved is positioned near the unique cluster Fe, able to react with the cluster. Our results explain how selective C-S bond cleavage is achieved in this radical SAM enzyme.
Journal of the American Chemical Society, Jan 22, 2017
The physical properties of a doped quantum dot (QD) are strongly influenced by the dopant site in... more The physical properties of a doped quantum dot (QD) are strongly influenced by the dopant site inside the host lattice, which determines the host-dopant coupling from the overlap between the dopant and exciton wave functions of the host lattice. Although several synthetic methodologies have been developed for introducing dopants inside the size-confined semiconductor nanocrystals, the controlled dopant-host lattice coupling by dopant migration is still unexplored. In this work, the effect of lattice mismatch of CdS/ZnS core/shell QDs on Mn(II) dopant behavior was studied. It was found that the dopant migration toward the alloyed interface of core/shell QDs is a thermodynamically driven process to minimize the lattice strain within the nanocrystals. The dopant migration rate could be represented by the Arrhenius equation and therefore can be controlled by the temperature and lattice mismatch. Furthermore, the energy transfer between host CdS QDs and dopants can be finely turned in a ...
Journal of the American Chemical Society, Apr 6, 2017
S-adenosylmethionine (SAM) has a sulfonium ion with three distinct C-S bonds. Conventional radica... more S-adenosylmethionine (SAM) has a sulfonium ion with three distinct C-S bonds. Conventional radical SAM enzymes use a [4Fe-4S] cluster to homolytically cleave the C5',adenosine-S bond of SAM to generate a 5'-deoxyadenosyl radical, which catalyz-es various downstream chemical reactions. Radical SAM en-zymes involved in diphthamide biosynthesis, such as Pyrococ-cus horikoshii Dph2 (PhDph2) and yeast Dph1-Dph2 instead cleave the Cγ,Met-S bond of methionine to generate the 3-amino-3-carboxylpropyl radical. We here show that radical SAM enzymes can be tuned to cleave the third C-S bond to the sulfonium sulfur by changing the structure of SAM. With a decarboxyl SAM analog (dc-SAM), PhDph2 cleaves the Cmethyl-S bond, forming 5'-deoxy-5'-(3-aminopropylthio) adenosine (dAPTA, 1). The methyl cleavage activity, like the cleavage of the other two C-S bonds, is dependent on the presence of a [4Fe-4S]+ cluster. Electron-nuclear double resonance (ENDOR) and mass spectroscopy data su...
Cholesterol is a ubiquitous component of eukaryotic cell membranes and a key molecule in controll... more Cholesterol is a ubiquitous component of eukaryotic cell membranes and a key molecule in controlling membrane fluidity, packing state, and various biological processes. It also plays a regulatory function in the immune response and antibiotic drug resistance by augmenting the membrane mechanical properties against structural damage. While it is well understood that, structurally, cholesterol exhibits a universal condensing effect on lipid membranes, its effects on membrane mechanics are assumed to be non-universal; i.e. cholesterol causes noticeable stiffening in saturated lipid membranes, but is surprisingly reported to have no stiffening effect on unsaturated lipid membranes such as DOPC. Here, using neutron spin-echo (NSE) spectroscopy, solid-state deuterium nuclear magnetic resonance (2H-NMR) spectroscopy, and molecular dynamics (MD) simulations, we report that, on the mesoscale, cholesterol increases the bending rigidity of DOPC membranes, similar to saturated membranes, throug...
CW saturation experiments are widely used in ESR studies of relaxation processes in proteins and ... more CW saturation experiments are widely used in ESR studies of relaxation processes in proteins and lipids. We develop the theory of saturation in ESR spectra in terms of its close relation with that of 2D-ELDOR. Our treatment of saturation is then based on the microscopic order macroscopic disorder (MOMD) model and can be used to fit the full CW saturation spectrum, rather than fitting just the peak–peak amplitude as a function of microwave field $$B_1$$ B 1 as is commonly done. This requires fewer experiments to yield effects on $$T_1$$ T 1 , as well as provides a more extensive dynamic structural picture, for example, for scanning experiments on different protein sites. The code is released as a publicly available software package in Python that can be used to fit CW saturation spectra from biological samples of interest.
Proceedings of the National Academy of Sciences, 2020
Significance Cholesterol regulates critical cell functions, including lysis, viral budding, and a... more Significance Cholesterol regulates critical cell functions, including lysis, viral budding, and antibiotic resistance, by modifying the bending rigidity of cell membranes; i.e., the ability of membranes to bend or withstand mechanical stresses. A molecular-level understanding of these functions requires knowledge of how cholesterol modifies membrane mechanics over relevant length and time scales. Currently, it is widely accepted that cholesterol has no effect on the mechanical properties of unsaturated lipid membranes, implying that viruses, for example, can bud from regions enriched in (poly)unsaturated lipids. Our observations that cholesterol causes local stiffening in DOPC membranes indicate that a reassessment of existing concepts is necessary. These findings have far-reaching implications in understanding cholesterol’s role in biology and its applications in bioengineering and drug design.
Transition metal ion doped one-dimensional (1-D) nanocrystals (NCs) have advantages of larger abs... more Transition metal ion doped one-dimensional (1-D) nanocrystals (NCs) have advantages of larger absorption cross sections and polarized absorption and emissions in comparison to 0-D NCs. However, direct synthesis of doped 1-D nanorods (NRs) or nanowires (NWs) has proven challenging. In this study, we report the synthesis of 1-D Mn-doped ZnSe NWs using a colloidal hot-injection method and shell passivation for core/shell NWs with tunable optical properties. Experimental results show optical properties of the NWs are controlled by the composition and thickness of the shell lattice. It was found that both the host-Mn energy transfer and Mn-Mn coupling are strongly dependent on the type of alloy at the interface of doped core/shell NWs. For Mn-doped type I ZnSe/ZnS core/shell NWs, the ZnS shell passivation can enhance florescence quantum yield with little effect on the location of the incorporated Mn dopant due to the identical cationic Zn site available for Mn dopants throughout the core...
Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed by a radical S-... more Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed by a radical S-adenosylmethionine (SAM) enzyme that cleaves a carbon-sulfur (C-S) bond in SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. Using rapid freezing, we have captured an organometallic intermediate with an iron-carbon (Fe-C) bond between ACP and the enzyme's [4Fe-4S] cluster. In the presence of the substrate protein, elongation factor 2, this intermediate converts to an organic radical, formed by addition of the ACP radical to a histidine side chain. Crystal structures of archaeal diphthamide biosynthetic radical SAM enzymes reveal that the carbon of the SAM C-S bond being cleaved is positioned near the unique cluster Fe, able to react with the cluster. Our results explain how selective C-S bond cleavage is achieved in this radical SAM enzyme.
Journal of the American Chemical Society, Jan 22, 2017
The physical properties of a doped quantum dot (QD) are strongly influenced by the dopant site in... more The physical properties of a doped quantum dot (QD) are strongly influenced by the dopant site inside the host lattice, which determines the host-dopant coupling from the overlap between the dopant and exciton wave functions of the host lattice. Although several synthetic methodologies have been developed for introducing dopants inside the size-confined semiconductor nanocrystals, the controlled dopant-host lattice coupling by dopant migration is still unexplored. In this work, the effect of lattice mismatch of CdS/ZnS core/shell QDs on Mn(II) dopant behavior was studied. It was found that the dopant migration toward the alloyed interface of core/shell QDs is a thermodynamically driven process to minimize the lattice strain within the nanocrystals. The dopant migration rate could be represented by the Arrhenius equation and therefore can be controlled by the temperature and lattice mismatch. Furthermore, the energy transfer between host CdS QDs and dopants can be finely turned in a ...
Journal of the American Chemical Society, Apr 6, 2017
S-adenosylmethionine (SAM) has a sulfonium ion with three distinct C-S bonds. Conventional radica... more S-adenosylmethionine (SAM) has a sulfonium ion with three distinct C-S bonds. Conventional radical SAM enzymes use a [4Fe-4S] cluster to homolytically cleave the C5',adenosine-S bond of SAM to generate a 5'-deoxyadenosyl radical, which catalyz-es various downstream chemical reactions. Radical SAM en-zymes involved in diphthamide biosynthesis, such as Pyrococ-cus horikoshii Dph2 (PhDph2) and yeast Dph1-Dph2 instead cleave the Cγ,Met-S bond of methionine to generate the 3-amino-3-carboxylpropyl radical. We here show that radical SAM enzymes can be tuned to cleave the third C-S bond to the sulfonium sulfur by changing the structure of SAM. With a decarboxyl SAM analog (dc-SAM), PhDph2 cleaves the Cmethyl-S bond, forming 5'-deoxy-5'-(3-aminopropylthio) adenosine (dAPTA, 1). The methyl cleavage activity, like the cleavage of the other two C-S bonds, is dependent on the presence of a [4Fe-4S]+ cluster. Electron-nuclear double resonance (ENDOR) and mass spectroscopy data su...
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Papers by Boris Dzikovski