Publications by authors named "Dmitriy Smolensky"

15 Publications

  • Page 1 of 1

Adverse effect of polystyrene microplastics (PS-MPs) on tube formation and viability of human umbilical vein endothelial cells.

Food Chem Toxicol 2021 Aug 19;154:112356. Epub 2021 Jun 19.

Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD, 20742, USA. Electronic address:

Environmental contamination by microplastics (MPs) is an emerging concern in recent years due to associated adverse impacts of MPs on potential human health problems. Endothelial dysfunction is a condition in which the endothelial layer fails to form normally, and is associated with impaired vascular function. Despite the fact that MPs are known to enter the circulation system through intestinal epithelium, little has been known whether MPs impact the normal function of endothelial cells and the formation of vasculature. In the current study, we investigated the effect of polystyrene microplastics (PS-MPs) on tube formation and cytotoxicity in human umbilical vein endothelial cells (HUVECs). Our study showed that the treatment of HUVECs with PS-MPs significantly decreased cell viability, with intracellular accumulation occurring in a dose- and size-dependent manner. Moreover, significant dose-dependent inhibition of angiogenic tube formation was observed in HUVECs treated with 0.5 μm PS-MPs; this effect was accompanied by suppression of angiogenic signaling pathways and inhibitory activity against wound healing and cell migration. Regarding the mechanism of decreased viability, we observed increased autophagic and necrotic cell death. These results indicate that 6-h exposure of endothelial cells to PS-MPs represses tube-forming capacity, while 48-h exposure leads to autophagy and necrosis-mediated cytotoxicity.
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http://dx.doi.org/10.1016/j.fct.2021.112356DOI Listing
August 2021

Antimicrobial Activity of Sorghum Phenolic Extract on Bovine Foodborne and Mastitis-Causing Pathogens.

Antibiotics (Basel) 2021 May 17;10(5). Epub 2021 May 17.

Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS 66506, USA.

Antimicrobial resistance in bacterial pathogens associated with bovine mastitis and human foodborne illnesses from contaminated food and water have an impact on animal and human health. Phenolic compounds have antimicrobial properties and some specialty sorghum grains are high in phenolic compounds, and the grain extract may have the potential as a natural antimicrobial alternative. The study's objective was to determine antimicrobial effects of sorghum phenolic extract on bacterial pathogens that cause bovine mastitis and human foodborne illnesses. Bacterial pathogens tested included , Typhimurium, , , , , , , and . Antibacterial activities of sorghum phenolic extracts were determined by agar-well diffusion assay. Sorghum phenolic extract was added to the wells in concentrations of 0, 100, 200, 500, 1000, or 4000 µg/mL. The control wells did not receive phenolic extract. Plates were incubated for 18-24 h, and the diameter of each zone of inhibition was measured. The results indicated that sorghum phenolic extract had inhibitory effects on , , , and .
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http://dx.doi.org/10.3390/antibiotics10050594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156376PMC
May 2021

Sorghum Phenolic Compounds Are Associated with Cell Growth Inhibition through Cell Cycle Arrest and Apoptosis in Human Hepatocarcinoma and Colorectal Adenocarcinoma Cells.

Foods 2021 May 1;10(5). Epub 2021 May 1.

Department of Food Nutrition Dietetics and Health, Kansas State University, Manhattan, KS 66506, USA.

Phenolic compounds in some specialty sorghums have been associated with cancer prevention. However, direct evidence and the underlying mechanisms for this are mostly unknown. In this study, phenolics were extracted from 13 selected sorghum accessions with black pericarp while F10000 hybrid with white pericarp was used as a control, and cell growth inhibition was studied in hepatocarcinoma HepG2 and colorectal adenocarcinoma Caco-2 cells. Total phenolic contents of the 13 high phenolic grains, as determined by Folin-Ciocalteu, were 30-64 mg GAE/g DW in the phenolic extracts of various accessions compared with the control F10000 at 2 mg GAE/g DW. Treatment of HepG2 with the extracted phenolics at 0-200 μM GAE up to 72 h resulted in a dose- and time-dependent reduction in cell numbers. The values of IC varied from 85 to 221 mg DW/mL while the control of F10000 was 1275 mg DW/mL. The underlying mechanisms were further examined using the highest phenolic content of PI329694 and the lowest IC of PI570481, resulting in a non-cytotoxic decrease in cell number that was significantly correlated with increased cell cycle arrest at G2/M and apoptotic cells in both HepG2 and Caco-2 cells. Taken together, these results indicated, for the first time, that inhibition of either HepG2 or Caco-2 cell growth by phenolic extracts from 13 selected sorghum accessions was due to cytostatic and apoptotic but not cytotoxic mechanisms, suggesting some specialty sorghums are a valuable, functional food, providing sustainable phenolics for potential cancer prevention.
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http://dx.doi.org/10.3390/foods10050993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147257PMC
May 2021

A Comparative Study on Phenolic Content, Antioxidant Activity and Anti-Inflammatory Capacity of Aqueous and Ethanolic Extracts of Sorghum in Lipopolysaccharide-Induced RAW 264.7 Macrophages.

Antioxidants (Basel) 2020 Dec 18;9(12). Epub 2020 Dec 18.

Center for Grain and Animal Health Research, USDA-ARS, Manhattan, KS 66502, USA.

Sorghum is an important cereal with diverse phenolic compounds that have potential health promoting benefits. The current study comparatively characterized the phenolic contents of two novel black-seeded sorghum lines (SC84 and PI570481) using different extraction systems (water, ethanol and their acidified counterparts) and evaluated their antioxidant and anti-inflammatory activities. Phenolic compositions were determined by spectrophotometric assays and HPLC analysis. Antioxidant activities were assessed by radical scavenging effects on nitric oxide (NO) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals, and the oxygen radical absorbance capacity (ORAC). Anti-inflammatory capacity was estimated by measuring levels of pro-inflammatory markers produced by lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Results showed that effects of solvent types and HCl on extraction efficiency differed among phenolic compounds and sorghum samples. Tannins were the most dominant polyphenols in the studied extracts (11.11-136.11 mg epicatechin equivalent/g sorghum). Sorghum extracts exerted more potent scavenging activity on DPPH than NO radicals. In LPS-activated RAW264.7 cells, sorghum extracts dose-dependently inhibited the production of NO, interleukin-6 (IL-6), and intracellular reactive oxygen species (ROS), with ethanolic extracts showing greater anti-inflammatory activity. Positive correlations were noted between tannin content and DPPH radical scavenging activity, and anti-inflammatory capacity. These results suggest the potential role of tannin-rich sorghum extracts against inflammation and associated diseases.
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http://dx.doi.org/10.3390/antiox9121297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767246PMC
December 2020

A mechanistic review: potential chronic disease-preventive properties of sorghum.

J Sci Food Agric 2021 May 22;101(7):2641-2649. Epub 2020 Nov 22.

Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD, USA.

Sorghum is one of the most widely cultivated crops, and is used in foods, domestic animal feedstuffs, alcohol production, and biofuels. Recently, many research groups have demonstrated that sorghum contains various components that are strongly associated with the prevention of major human chronic diseases such as obesity, diabetes, atherosclerosis, cancer, and inflammation. However, to use sorghum more widely as a food for the potential prevention and treatment of human chronic diseases, more studies will be required to elucidate the biological mechanisms. In this review paper, we highlight multiple findings to propose a mechanistic link between sorghum consumption and reduced risk of chronic diseases. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.10933DOI Listing
May 2021

Anticancer Activity of a Novel High Phenolic Sorghum Bran in Human Colon Cancer Cells.

Oxid Med Cell Longev 2020 2;2020:2890536. Epub 2020 Oct 2.

Agricultural Research Service, U.S. Department of Agriculture, Center for Grain and Animal Health Research, Manhattan, KS 66502, USA.

Human colon cancer is the third leading cause of mortality in the United States and worldwide. Chemoprevention using diet is widely accepted as a promising approach for cancer management. Numerous population studies indicate a negative correlation between the incidence of colon cancer and consumption of whole grains with a high content of bioactive phenolic compounds. In the current study, we evaluated the anticancer properties of a high phenolic sorghum bran extract prepared using 70% ethanol with 5% citric acid solvent at room temperature. A significant dose-dependent suppression of cell proliferation was observed in human colon cancer cells treated with the high phenolic sorghum bran extract. Apoptosis and S phase growth arrest were induced, while cell migration and invasion were inhibited by this treatment; these effects were accompanied by altered expression of apoptosis, cell cycle, and metastasis-regulating genes. We also found that the high phenolic sorghum bran extract stimulated DNA damage in association with induction of extracellular signal-regulated kinase (ERK) and c-Jun-NH-terminal kinase (JNK) and subsequent expression of activating transcription factor 3 (ATF3). The present study expands our understanding of the potential use of high phenolic sorghum bran to prevent human colon cancer.
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http://dx.doi.org/10.1155/2020/2890536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556115PMC
May 2021

Potential benefits of patchouli alcohol in prevention of human diseases: A mechanistic review.

Int Immunopharmacol 2020 Dec 8;89(Pt A):107056. Epub 2020 Oct 8.

Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD 20742, USA. Electronic address:

Patchouli alcohol (PA), a tricyclic sesquiterpene, is a dominant bioactive component in oil extracted from the aerial parts of Pogostemon cablin (patchouli). Diverse beneficial activities have been reported, including anti-influenza virus, anti-depressant, anti-nociceptive, vasorelaxation, lung protection, brain protection, anti-ulcerogenic, anti-colitis, pre-biotic-like, anti-inflammatory, anti-cancer and protective activities against metabolic diseases. However, detailed mechanistic studies are required to explore the possibility of developing PA as a functional food material or promising drug for the prevention and treatment of human diseases. This review highlights multiple molecular targets and working mechanisms by which PA mediates health benefits.
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http://dx.doi.org/10.1016/j.intimp.2020.107056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543893PMC
December 2020

High-polyphenol extracts from Sorghum bicolor attenuate replication of Legionella pneumophila within RAW 264.7 macrophages.

FEMS Microbiol Lett 2020 04;367(7)

Division of Biology, Kansas State University, 1717 Claflin Road, Manhattan, Kansas, 66506 USA.

Polyphenols derived from a variety of plants have demonstrated antimicrobial activity against diverse microbial pathogens. Legionella pneumophila is an intracellular bacterial pathogen that opportunistically causes a severe inflammatory pneumonia in humans, called Legionnaires' Disease, via replication within macrophages. Previous studies demonstrated that tea polyphenols attenuate L. pneumophila intracellular replication within mouse macrophages via increased tumor necrosis factor (TNF) production. Sorghum bicolor is a sustainable cereal crop that thrives in arid environments and is well-suited to continued production in warming climates. Sorghum polyphenols have anticancer and antioxidant properties, but their antimicrobial activity has not been evaluated. Here, we investigated the impact of sorghum polyphenols on L. pneumophila intracellular replication within RAW 264.7 mouse macrophages. Sorghum high-polyphenol extract (HPE) attenuated L. pneumophila intracellular replication in a dose-dependent manner but did not impair either bacterial replication in rich media or macrophage viability. Moreover, HPE treatment enhanced both TNF and IL-6 secretion from L. pneumophila infected macrophages. Thus, polyphenols derived from sorghum enhance macrophage restriction of L. pneumophila, likely via increased pro-inflammatory cytokine production. This work reveals commonalities between plant polyphenol-mediated antimicrobial activity and provides a foundation for future evaluation of sorghum as an antimicrobial agent.
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http://dx.doi.org/10.1093/femsle/fnaa053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023677PMC
April 2020

Evaluation of ethanol-based extraction conditions of sorghum bran bioactive compounds with downstream anti-proliferative properties in human cancer cells.

Heliyon 2019 May 7;5(5):e01589. Epub 2019 May 7.

Grain Quality and Structure Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Manhattan, KS, USA.

Certain foods such as turmeric and green tea have been extensively studied for anticancer properties, while high polyphenol sorghum has not received the same attention. Some bioactive compounds in with anticancer activity have been identified, indicating the further need for research and screening methods of high polyphenol sorghum varieties. This study was aimed at improving the extraction of sorghum bioactive compounds by using food-grade solvents using ethanol and citric acid. We used three sorghum varieties and green tea (GT) as a control. The extraction methods were screened for anti-proliferative properties in HepG2 and HCT-15 cancer cell lines, using a cell viability assay. Extraction conditions were improved for anti-proliferative compounds from a high-phenolic sorghum variety (HP), sumac sorghum (CS), and GT. HP was more effective at inhibiting cell viability than CB, CS, and GT. The results demonstrate an efficient method for extracting sorghum bioactive compounds for future anticancer research using food approved ingredients.
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http://dx.doi.org/10.1016/j.heliyon.2019.e01589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512580PMC
May 2019

High-Polyphenol Sorghum Bran Extract Inhibits Cancer Cell Growth Through ROS Induction, Cell Cycle Arrest, and Apoptosis.

J Med Food 2018 Oct 7;21(10):990-998. Epub 2018 May 7.

1 Arthropod-Borne Animal Diseases Research Unit, Agricultural Research Service , U.S. Department of Agriculture, Manhattan, Kansas, USA .

As diet is one of the major controllable factors in cancer development, potentially chemopreventive foods are of significant interest to public health. One such food is sorghum (Sorghum bicolor), a cereal grain that contains varying concentrations of polyphenols. In a panel of 15 sorghum germplasm, we identified strains with higher polyphenol content than previously reported for this grain. Bran extracts from the germplasm with the highest and lowest polyphenol content were then tested against HepG2 and Caco2 cancer cells to assess effects on cancer cell viability, reactive oxygen species, apoptosis, DNA damage, cell cycle arrest, and protein expression patterns. High-polyphenol extracts, but not low-polyphenol extracts, reduced cell viability by inducing apoptosis and cell cycle arrest following production of reactive oxygen species and oxidative DNA damage. The results indicate that high-polyphenol sorghum bran extracts have potential anticancer properties and warrant further research, not only to test against specific cancers but also to elucidate underlying mechanisms of action.
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http://dx.doi.org/10.1089/jmf.2018.0008DOI Listing
October 2018

Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer.

Drug Des Devel Ther 2016 5;10:3305-3322. Epub 2016 Oct 5.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine; UT-ORNL Graduate School of Genome Science and Technology, The University of Tennessee, Knoxville, TN, USA.

Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer.
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http://dx.doi.org/10.2147/DDDT.S112113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063594PMC
April 2017

Inhibition of the PI3K/AKT Pathway Sensitizes Oral Squamous Cell Carcinoma Cells to Anthracycline-Based Chemotherapy In Vitro.

J Cell Biochem 2017 09 16;118(9):2615-2624. Epub 2017 May 16.

UT-ORNL Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, 37996, Tennessee.

Anthracycline-based chemotherapy, such as doxorubicin (Dox), while effective against many solid tumors, is not widely used for head and neck cancers. In this study, we evaluated the efficacy of Dox, and its derivative AD198 in human, canine, and feline oral squamous cell carcinomas cells (OSCC) in vitro. Dox and AD198 had significant an anti-proliferative effect on human, canine, and feline OSCC cells in dose-dependent manner. AD198 inhibited cell proliferation more effectively than Dox in tested OSCC cells. In the human oral squamous cell carcinoma SCC25 cells, Dox and AD198 increased the production of reactive oxygen species and subsequently increased apoptosis through activation of caspase signaling pathway. Dox and AD198 increased activation of AKT, ERK1/2, and p38 MAPK signaling pathways in tested OSCC cells by dose-dependent manner. The efficacy of Dox and AD198 treatments in inhibition of cell proliferation was increased in tested OSCC when combined with PI3K/AKT inhibitor, LY294002 treatment. Inhibition of PI3K/AKT reduced Dox- and AD198-induced activation of ERK1/2 and further increased Dox- and AD198-induced phosphorylation of p38 MAPK in OSCC. Our results suggest that the anthracycline therapies, such as Dox or AD198, can be more effective for treatment of OSCC when combined with inhibitors of the PI3K/AKT pathway. J. Cell. Biochem. 118: 2615-2624, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jcb.25747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572634PMC
September 2017

Phosphatidylinositol- 3-kinase inhibitor induces chemosensitivity to a novel derivative of doxorubicin, AD198 chemotherapy in human bladder cancer cells in vitro.

BMC Cancer 2015 Nov 23;15:927. Epub 2015 Nov 23.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, 2407 River Drive A122, Knoxville, TN, 37996, USA.

Background: Doxorubicin (Dox) is widely used to treat progressed bladder cancer after transurethral resection. The use of Dox-chemotherapy has been limited due to induced drug resistance and cumulative cardiotoxic effects. N-benzyladriamycin-14-valerate (AD198), a novel derivative of Dox, has a potential to become a more effective treatment than Dox by overcoming drug resistance and cardio-toxicity as shown in the rodent model of lymphoma in vivo. The purpose of this study was to compare the efficacy of Dox and AD198 and explore their mechanisms in inhibition on human bladder cancer cells in vitro.

Methods: We evaluated the effects of Dox and AD198 on cell viability of human transitional cell carcinoma (TCC) cell lines T24 and UMUC3 by MTS assay in vitro. The effects of Dox and AD198 on cell apoptosis were determined by caspase 3/7 assay, generation of reactive oxygen species (ROS), and Western Blotting (WB) analysis.

Results: AD198 was more effective than Dox in inhibition of cell viability of T24 and UMUC3 cells in vitro. Both Dox and AD198 significantly increased the generation of ROS and induced apoptosis in caspase-dependent and -independent manner in T24 and UMUC3 cells. AD 198 induced significantly higher production of ROS as compared to Dox in human TCC cells. Dox and AD198 activated the pro-apoptotic p38 MAPK pathway; however, on the other hand also increased phosphorylation of AKT, an anti-apoptotic signaling pathway, in T24 and UMUC3 cells. Combined treatment of PI3K inhibitor (LY294002) with Dox or AD198 inhibited cell viability of T24 and UMUC3 cells more effectively than any of drug treatments alone.

Conclusions: These data suggest that AD198 as novel derivative of Dox, could be a used as effective treatment for bladder cancer. Dox and AD198 induced PI3K/AKT signaling pathway that is a one of the indicators of pro-survival and possible drug-resistance mechanisms of chemotherapies in bladder cancer. Combined therapies of Dox or AD198 with inhibitors of PI3K/AKT signaling pathway might lead to more effective treatment outcome for patients diagnosed with bladder cancer based on our in vitro experiments.
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http://dx.doi.org/10.1186/s12885-015-1930-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4657321PMC
November 2015

A novel COX-independent mechanism of sulindac sulfide involves cleavage of epithelial cell adhesion molecule protein.

Exp Cell Res 2014 Aug 22;326(1):1-9. Epub 2014 May 22.

Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA; Genome Science Technology, University of Tennessee, Knoxville, TN, USA. Electronic address:

Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively used over the counter to treat headaches and inflammation as well as clinically to prevent cancer among high-risk groups. The inhibition of cyclooxygenase (COX) activity by NSAIDs plays a role in their anti-tumorigenic properties. NSAIDs also have COX-independent activity which is not fully understood. In this study, we report a novel COX-independent mechanism of sulindac sulfide (SS), which facilitates a previously uncharacterized cleavage of epithelial cell adhesion molecule (EpCAM) protein. EpCAM is a type I transmembrane glycoprotein that has been implemented as an over-expressed oncogene in many cancers including colon, breast, pancreas, and prostate. We found EpCAM to be down-regulated by SS in a manner that is independent of COX activity, transcription regulation, de novo protein synthesis, and proteasomal degradation pathway. Our findings clearly demonstrate that SS drives cleavage of the extracellular portion of EpCAM near the N-terminus. This SS driven cleavage is blocked by a deleting amino acids 55-81 as well as simply mutating arginine residues at positions 80 and 81 to alanine of EpCAM. Proteolysis of EpCAM by SS may provide a novel mechanism by which NSAIDs affect anti-tumorigenesis at the post-translational level.
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http://dx.doi.org/10.1016/j.yexcr.2014.05.009DOI Listing
August 2014

Insight into the structure of light-harvesting complex II and its stabilization in detergent solution.

J Phys Chem B 2009 Dec;113(51):16377-83

Center for Structural Molecular Biology, Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA.

The structure of spinach light-harvesting complex II (LHC II), stabilized in a solution of the detergent n-octyl-beta-D-glucoside (BOG), was investigated by small-angle neutron scattering (SANS). Physicochemical characterization of the isolated complex indicated that it was pure (>95%) and also in its native trimeric state. SANS with contrast variation was used to investigate the properties of the protein-detergent complex at three different H(2)O/D(2)O contrast match points, enabling the scattering properties of the protein and detergent to be investigated independently. The topological shape of LHC II, determined using ab initio shape restoration methods from the SANS data at the contrast match point of BOG, was consistent with the X-ray crystallographic structure of LHC II (Liu et al. Nature 2004 428, 287-292). The interactions of the protein and detergent were investigated at the contrast match point for the protein and also in 100% D(2)O. The data suggested that BOG micelle structure was altered by its interaction with LHC II, but large aggregate structures were not formed. Indirect Fourier transform analysis of the LHC II/BOG scattering curves showed that the increase in the maximum dimension of the protein-detergent complex was consistent with the presence of a monolayer of detergent surrounding the protein. A model of the LHC II/BOG complex was generated to interpret the measurements made in 100% D(2)O. This model adequately reproduced the overall size of the LHC II/BOG complex, but demonstrated that the detergent does not have a highly regular shape that surrounds the hydrophobic periphery of LHC II. In addition to demonstrating that natively structured LHC II can be produced for functional characterization and for use in artificial solar energy applications, the analysis and modeling approaches described here can be used for characterizing detergent-associated alpha-helical transmembrane proteins.
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http://dx.doi.org/10.1021/jp905050bDOI Listing
December 2009
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