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2.
RSC Adv ; 10(30): 17673-17680, 2020 May 05.
Article in English | MEDLINE | ID: mdl-35515618

ABSTRACT

Poly(3,4-ethylenedioxythiophene)polystyrene sulfonate (PEDOT:PSS) is often used as a hole injection and extractor for various organic electronic devices. This study investigated whether it is possible to n-dope PEDOT:PSS with barium acetylacetonate (Ba(acac)2) to change its work function so that to be more suitable for electron injection and extraction. Molecular dynamics simulations suggested that barium cations can interact with the aromatic rings of PEDOT and the negatively charged sulfonate in PSS. At high doping concentration, we found that PEDOT became dedoped and precipitated resulting in a clear solution after filtration. The absence of the absorption peak of PEDOT at 263 nm indicates the removal of PEDOT after filtration. The shift in O 1s to a lower binding energy as seen in X-ray photoelectron spectroscopy suggested that the polystyrene sulfonic acids are being ionized to form barium polystyrene sulfonate (Ba-PSS). By spin-coating the solution on top of indium tin oxide, the work function can be adjusted to as low as 3.6 eV. The ability of such a mixture to inject and extract electrons is demonstrated using 2,7-bis(diphenylphosphoryl)-9,9'-spirobifluorene as an electron transporting layer. We attributed the lowering of the work function as the result of the formation of an interfacial dipole as large as 1.37 eV at the ITO/Ba-PSS interface.

3.
Microb Pathog ; 124: 266-271, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30138755

ABSTRACT

Obesity and obesity-related comorbidities have transformed into a global epidemic. The number of people suffering from obesity has increased dramatically within the past few decades. This rise in obesity cannot alone be explained by genetic factors; however, diet, environment, lifestyle, and presence of other diseases undoubtedly contribute towards obesity etiology. Nevertheless, evidence suggests that alterations in the gut microbial diversity and composition have a role to play in energy assimilation, storage, and expenditure. In this review, the impact of gut microbiota composition on metabolic functionalities, and potential therapeutics such as gut microbial modulation to manage obesity and its associated comorbidities are highlighted. Optimistically, an understanding of the gut microbiome could facilitate the innovative clinical strategies to restore the normal gut flora and improve lifestyle-related diseases in the future.


Subject(s)
Gastrointestinal Microbiome , Obesity/microbiology , Animals , Comorbidity , Gastrointestinal Tract/metabolism , Gastrointestinal Tract/microbiology , Humans , Obesity/epidemiology , Obesity/metabolism
4.
Front Microbiol ; 9: 1021, 2018.
Article in English | MEDLINE | ID: mdl-29867905

ABSTRACT

This study was designed to evaluate the protective effect of ethanol extract (SEL001) isolated from a potent probiotic strain Lactobacillus sakei proBio-65 on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model. Histopathological and histomorphometrical changes in the ear and dorsal skin tissues were observed under hematoxylin and eosin stain for general histopathological architectures or Masson's trichrome stain for collagen fibers. The expression profile of psoriasis-associated specific genes was determined using Real-Time PCR analysis. As a result, topical application of IMQ resulted in a significant increase of mean total and epithelial (epidermis) thicknesses, the number of inflammatory cells infiltrated in the dermis, and the decrease of dermis collagen fiber occupied regions in the ear tissues of IMQ and IMQ plus vaseline treated groups when compared to the intact control group. A significant increase of epithelial thickness and number of inflammatory cells infiltrated in the dermis of dorsal skin tissues were also noticed in IMQ and IMQ plus vaseline treated groups as compared to the intact control group, suggesting classic IMQ-induced hypersensitive psoriasis. IMQ-induced hypersensitive psoriasis related histopathological changes to the ear and dorsal skin tissues were significantly inhibited by the treatment of a standard drug clobetasol and SEL001. Further, mRNA expression analysis indicated a significant increase in gene expression levels of pro-inflammatory cytokines, including IL-19, IL-17A, and IL-23 in IMQ and IMQ plus vaseline treated groups than that of the control. Clobetasol and SEL001 treated groups resulted in a lower gene expression level of IL-19, IL-17A, and IL-23 as compared to IMQ and IMQ plus vaseline treated groups. These results enforce that SEL001 could be a novel treatment for psoriasis and an alternative to other drugs that pose a number of side effects on the skin.

5.
Front Pharmacol ; 8: 830, 2017.
Article in English | MEDLINE | ID: mdl-29204118

ABSTRACT

Food contamination is a matter of serious concern, as the high concentration of chemicals present in the edibles poses serious health risks. Protecting the public from the degrees of the harmfulness of contaminated foods has become a daunting task. This article highlights the causes, types, and health implications of chemical contamination in food. The food contamination could be due to naturally occurring contaminants in the environment or artificially introduced by the human. The phases of food processing, packaging, transportation, and storage are also significant contributors to food contamination. The implications of these chemical contaminants on human health are grave, ranging from mild gastroenteritis to fatal cases of hepatic, renal, and neurological syndromes. Although, the government regulates such chemicals in the eatables by prescribing minimum limits that are safe for human consumption yet measures still need to be taken to curb food contamination entirely. Therefore, a variety of food needs to be inspected and measured for the presence of chemical contaminants. The preventative measures pertaining about the food contaminants problems are pointed out and discussed.

6.
Front Microbiol ; 8: 1740, 2017.
Article in English | MEDLINE | ID: mdl-28900425

ABSTRACT

[This corrects the article on p. 1417 in vol. 8, PMID: 28798738.].

7.
Article in English | MEDLINE | ID: mdl-28791258

ABSTRACT

Dengue is currently the highest and rapidly spreading vector-borne viral disease, which can lead to mortality in its severe form. The globally endemic dengue poses as a public health and economic challenge that has been attempted to suppress though application of various prevention and control techniques. Therefore, broad spectrum techniques, that are efficient, cost-effective, and environmentally sustainable, are proposed and practiced in dengue-endemic regions. The development of vaccines and immunotherapies have introduced a new dimension for effective dengue control and prevention. Thus, the present study focuses on the preventive and control strategies that are currently employed to counter dengue. While traditional control strategies bring temporary sustainability alone, implementation of novel biotechnological interventions, such as sterile insect technique, paratransgenesis, and production of genetically modified vectors, has improved the efficacy of the traditional strategies. Although a large-scale vector control strategy can be limited, innovative vaccine candidates have provided evidence for promising dengue prevention measures. The use of tetravalent dengue vaccine (CYD-TDV) has been the most effective so far in treating dengue infections. Nonetheless, challenges and limitation hinder the progress of developing integrated intervention methods and vaccines; while the improvement in the latest techniques and vaccine formulation continues, one can hope for a future without the threat of dengue virus.


Subject(s)
Communicable Disease Control/methods , Dengue Vaccines/isolation & purification , Dengue/prevention & control , Animals , Communicable Disease Control/trends , Culicidae , Dengue Vaccines/immunology , Humans
8.
Front Microbiol ; 8: 1417, 2017.
Article in English | MEDLINE | ID: mdl-28798738

ABSTRACT

ZIKA virus (ZIKV) poses a severe threat to the world. Recent outbreaks of ZIKV after 2007 along with its quick transmission have made this virus a matter of international concern. The virus shows symptoms that are similar to those caused in the wake of dengue virus (DENV) and other flaviviruses, which makes it difficult to discern the viral infection. Diagnosis is further complicated as the virus cross-reacts with antibodies of other viruses. Currently, molecular diagnosis of the virus is being performed by RT-PCR and IgM-captured enzyme-linked immunosorbent assay (MAC-ELISA). The real brunt of the virus is, however, borne by children and adults alike. Case studies of the ZIKV outbreaks in the French Polynesia and other places have suggested that there is a close link between the ZIKV and Gullian-Barre syndrome (GBS). The GBS has closely followed in areas facing ZIKV outbreaks. Although solid evidence is yet to emerge, clinical data integration has revealed a large number of ZIKV patients having GBS. Moreover, the amniotic fluids, blood cord, and miscarriage tissues of mothers have been detected with ZIKV, which indicates that the virus either gets transferred from mother to fetus or seeks direct entry in the fetus, causing microcephaly and other brain anomalies in the newborn babies. Studies on mice have confirmed the link between the ZIKV infection during pregnancy and microcephaly in babies. Reports have highlighted the sexual transmission of the ZIKV, as it has been detected in the semen and saliva of affected persons. The intensity with which the ZIKA is spreading can collapse the health sector of several countries, which are poor. A comprehensive strategy is a need of an hour to combat this virus so as to prevent its transmission and avert the looming threat. At the same time, more research on the cure of the ZIKV is imperative.

9.
Front Microbiol ; 8: 804, 2017.
Article in English | MEDLINE | ID: mdl-28515721

ABSTRACT

This study was undertaken to assess the antibacterial potential of a polyphenolic compound (+)-lariciresinol isolated from Rubia philippinensis against selected foodborne pathogens Staphylococcus aureus KCTC1621 and Escherichia coli O157:H7. (+)-Lariciresinol at the tested concentrations (250 µg/disk) evoked a significant antibacterial effect as a diameter of inhibition zones (12.1-14.9 mm) with minimum inhibitory concentration (MIC), and minimum bactericidal concentration values of 125-250 and 125-250 µg/mL, respectively. Furthermore, (+)-lariciresinol at MIC showed reduction in bacterial cell viabilities, efflux of potassium (K+) ions and release of 260 nm materials against E. coli O157:H7 and S. aureus KCTC1621. Moreover, deteriorated cell wall morphology of E. coli O157:H7 and S. aureus KCTC1621 cells treated with (+)-lariciresinol at MIC further confirmed its inhibitory effect against the tested pathogens, suggesting it to be an alternative means of antimicrobials.

10.
Front Microbiol ; 8: 552, 2017.
Article in English | MEDLINE | ID: mdl-28400770

ABSTRACT

This study was undertaken to assess the antibacterial potential of 3,8-dihydroxyquinoline (jineol) isolated from Scolopendra subspinipes mutilans against selected foodborne pathogens Escherichia coli O157:H7 and Staphylococcus aureus KCTC-1621. Jineol at the tested concentration (50 µL; corresponding to 250 µg/disk) exhibited significant antibacterial effects as a diameter of inhibition zones (11.6-13.6 mm), along with minimum inhibitory concentration (MIC) and minimum bactericidal concentration values found in the range of (62.5-125 µg/mL) and (125-250 µg/mL), respectively. Jineol also exhibited significant antibacterial effects as confirmed by the reduction in bacterial cell viabilities, increasing release of potassium (K+) ions (650 and 700 mmole/L) and 260 nm materials (optical density: 2.98-3.12) against both the tested pathogens, E. coli O157:H7 and S. aureus KCTC-1621, respectively. Moreover, changes in the cell wall morphology of E. coli O157:H7 and S. aureus KCTC-1621 cells treated with jineol at MIC further confirmed its inhibitory potential against the tested pathogens, suggesting its role as an effective antimicrobial to control foodborne pathogens.

11.
J Phys Condens Matter ; 28(36): 365002, 2016 09 14.
Article in English | MEDLINE | ID: mdl-27390863

ABSTRACT

UNLABELLED: The interfacial properties between electrodes and the various organic layers that comprise an organic electronic device are of direct relevance in understanding charge injection, extraction and generation. The energy levels and energy-bending of three interfaces; indium tin oxide (ITO)/poly(3,4-ethylenedioxythiophene) polystyrene sulfonate ( PEDOT: PSS), ITO/poly(N-vinylcarbazole) (PVK) and PEDOT: PSS/PVK were measured using ultraviolet photoelectron spectroscopy (UPS) and x-ray photoelectron spectroscopy (XPS). By decoupling the vacuum shift and energy-bending, the energy-bending at these interfaces can be simulated using an electrostatic model that takes into account the energetic disorder of the polymers. The model is further extended to include blended mixtures of semiconductors at differing concentrations and it was found that a very good agreement exists between the experiment and theory for all interfaces. This suggests that the electrostatic model can be used to describe energy-bending at the interface between any organic semiconductors. Further investigation into the effect of the Gaussian density of states width on energy-bending is warranted.

12.
Front Microbiol ; 7: 507, 2016.
Article in English | MEDLINE | ID: mdl-27148196

ABSTRACT

Atopic dermatitis (AD) is a common, recurrent, chronic inflammatory skin disease that is a cause of considerable economic and social burden. Its prevalence varies substantially among different countries with an incidence rate proclaimed to reach up to 20% of children in developed countries and continues to escalate in developing nations. This increased rate of incidence has changed the focus of research on AD toward epidemiology, prevention, and treatment. The effects of probiotics in the prevention and treatment of AD remain elusive. However, evidence from different research groups show that probiotics could have positive effect on AD treatment, if any, that depend on multiple factors, such as specific probiotic strains, time of administration (onset time), duration of exposure, and dosage. However, till date we still lack strong evidence to advocate the use of probiotics in the treatment of AD, and questions remain to be answered considering its clinical use in future. Based on updated information, the processes that facilitate the development of AD and the topic of the administration of probiotics are addressed in this review.

13.
Proc Natl Acad Sci U S A ; 112(31): 9620-5, 2015 Aug 04.
Article in English | MEDLINE | ID: mdl-26203127

ABSTRACT

Acquired thrombotic thrombocytopenic purpura (TTP), a thrombotic disorder that is fatal in almost all cases if not treated promptly, is primarily caused by IgG-type autoantibodies that inhibit the ability of the ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) metalloprotease to cleave von Willebrand factor (VWF). Because the mechanism of autoantibody-mediated inhibition of ADAMTS13 activity is not known, the only effective therapy so far is repeated whole-body plasma exchange. We used hydrogen-deuterium exchange mass spectrometry (HX MS) to determine the ADAMTS13 binding epitope for three representative human monoclonal autoantibodies, isolated from TTP patients by phage display as tethered single-chain fragments of the variable regions (scFvs). All three scFvs bind the same conformationally discontinuous epitopic region on five small solvent-exposed loops in the spacer domain of ADAMTS13. The same epitopic region is also bound by most polyclonal IgG autoantibodies in 23 TTP patients that we tested. The ability of ADAMTS13 to proteolyze VWF is impaired by the binding of autoantibodies at the epitopic loops in the spacer domain, by the deletion of individual epitopic loops, and by some local mutations. Structural considerations and HX MS results rule out any disruptive structure change effect in the distant ADAMTS13 metalloprotease domain. Instead, it appears that the same ADAMTS13 loop segments that bind the autoantibodies are also responsible for correct binding to the VWF substrate. If so, the autoantibodies must prevent VWF proteolysis simply by physically blocking normal ADAMTS13 to VWF interaction. These results point to the mechanism for autoantibody action and an avenue for therapeutic intervention.


Subject(s)
Deuterium Exchange Measurement/methods , Epitope Mapping , Mass Spectrometry/methods , Purpura, Thrombotic Thrombocytopenic/pathology , Purpura, Thrombotic Thrombocytopenic/therapy , ADAM Proteins/blood , ADAM Proteins/chemistry , ADAM Proteins/metabolism , ADAMTS13 Protein , Adult , Aged , Amino Acid Sequence , Antigens/metabolism , Binding Sites , Binding, Competitive , Child , Demography , Epitopes/chemistry , Female , Humans , Immunoglobulin G/metabolism , Kinetics , Male , Middle Aged , Molecular Sequence Data , Protein Binding , Proteolysis , Sequence Alignment , Sequence Deletion , Single-Chain Antibodies/metabolism , Young Adult
15.
J Nanosci Nanotechnol ; 14(5): 3398-402, 2014 May.
Article in English | MEDLINE | ID: mdl-24734558

ABSTRACT

Here we report our findings on the removal of metallic single-walled carbon nanotubes using an aqueous two-phase system. The aqueous two-phase system contained as received carbon nanotubes, polyethylene glycol, dextran, N-methylpyrrolidone, cetyltrimethylammonium bromide, and water which phase separated into top and bottom phases. The top phase was dominated by polyethylene glycol whereas the bottom phase was dominated by dextran. The dextran-rich phase contained more semiconducting species while metallic species was more abundant in the polyethylene glycol rich-phase. It was found via Fourier-Transform Infrared Spectroscopy that cetyltrimethylammonium bromide only present in the dextran-rich phase. A selectivity mechanism is tentatively proposed and discussed.

16.
Acta Neurochir (Wien) ; 156(1): 153-7, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24292808

ABSTRACT

BACKGROUND: Entrapment neuropathy of the ulnar nerve at the level of the elbow is the shared domain of multiple surgical specialties. A wide variety of operative methods for its surgical management have been reported. Our hospital utilizes neurolysis (NL) and subcutaneous transposition (AST). The aim of this paper was to compare the clinical outcomes in patients treated by ulnar nerve transposition versus neurolysis over a 20-year period. METHODS: We included patients who underwent either neurolysis or an ulnar nerve transposition. A retrospective analysis was performed which included 480 patients at our institution between January 1992 and December 2012. In total, physical and electronic records for 480 patients were reviewed. Three-hundred and one underwent ulnar nerve transposition and 179 underwent ulnar nerve neurolysis . RESULTS: In the AST group 201/301 patients suffered from parasthesiae pre-operatively and 156/301 had pain at and around the cubital tunnel. Paresis of the ulnar nerve innervated muscles was present in 99/301 patients. At the 3-month follow-up appointment, 187/201 patients with parasthesiae and 113/156 patients with local pain had resolution of their symptoms. In the NL group 151/179 patients had parasthesiae pre-operatively and 126/179 had pain at and around the cubital tunnel. Paresis of the ulnar nerve innervated muscles was present in 56/179 patients. At the 3-month follow-up appointment, 141/151 patients with parasthesiae and 117/126 patients with local pain had resolution of their symptoms. CONCLUSIONS: In cases of ulnar nerve compression at the cubital tunnel, both neurolysis and transposition are effective in improving clinical outcome. The only statistically significant advantage of neurolysis over transposition seems to be relief of localized elbow pain. We recommend neurolysis as the preferred procedure.


Subject(s)
Cubital Tunnel Syndrome/surgery , Nerve Compression Syndromes/surgery , Neurosurgical Procedures , Ulnar Nerve/surgery , Adult , Aged , Aged, 80 and over , Cubital Tunnel Syndrome/diagnosis , Elbow/innervation , Elbow/surgery , Female , Humans , Male , Middle Aged , Nerve Compression Syndromes/diagnosis , Nerve Transfer/methods , Retrospective Studies , Treatment Outcome
17.
Sci Total Environ ; 458-460: 499-507, 2013 Aug 01.
Article in English | MEDLINE | ID: mdl-23697849

ABSTRACT

The burgeoning of municipal solid waste (MSW) disposal issue and climate change have drawn massive attention from people. On the one hand, Hong Kong is facing a controversial debate over the implementation of proposed landfill extension (LFE) and advanced incineration facility (AIF) to curb the MSW disposal issue. On the other hand, the Hong Kong Special Administrative Region Government is taking concerted efforts to reduce the carbon intensity in this region. This paper discusses the greenhouse gas (GHG) emissions from four proposed waste disposal scenarios, covering the proposed LFE and AIF within a defined system boundary. On the basis of the data collected, assumptions made, and system boundary defined in this study, the results indicate that AIF releases less GHG emissions than LFE. The GHG emissions from LFE are highly contributed by the landfill methane (CH4) emissions but offset by biogenic carbon storage, while the GHG emissions from AIF are mostly due to the stack discharge system but offset by the energy recovery system. Furthermore, parametric sensitivity analyses show that GHG emissions are strongly dependent on the landfill CH4 recovery rate, types of electricity displaced by energy recovery systems, and the heating value of MSW, altering the order of preferred waste disposal scenarios. This evaluation provides valuable insights into the applicability of a policy framework for MSW management practices in reducing GHG emissions.


Subject(s)
Air Pollutants/analysis , Conservation of Natural Resources/statistics & numerical data , Greenhouse Effect , Incineration/instrumentation , Refuse Disposal/instrumentation , Waste Disposal Facilities/instrumentation , Hong Kong , Incineration/statistics & numerical data , Models, Theoretical , Refuse Disposal/statistics & numerical data , Waste Disposal Facilities/statistics & numerical data
18.
Diabet Med ; 30(9): 1067-74, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23600479

ABSTRACT

AIMS: To measure serum pigment epithelium-derived factor in control subjects with normal fasting glucose, and in subjects with impaired fasting glucose and those with newly diagnosed Type 2 diabetes, before treatment initiation, and to measure pigment epithelium-derived factor prospectively in patients being treated with HDL-raising therapy, niacin. METHODS: We enrolled 89 individuals attending an institutional health screen. Biochemical indices including lipids, homeostasis model assessment-insulin resistance, high-sensitivity C-reactive protein and pigment epithelium-derived factor were analysed in fasting blood. To validate the association between HDL and pigment epithelium-derived factor, we analysed samples from a separate study cohort with low HDL, followed up for 12-weeks while on niacin treatment. Secreted pigment epithelium-derived factor from 3T3-L1 adipocytes, after HDL treatment (24-h), was measured using Western blot analysis. RESULTS: Mean (± sd) serum pigment epithelium-derived factor was significantly higher in subjects with impaired fasting glucose [13.99 (± 3.06) µg/ml] and Type 2 diabetes [12.94 (± 2.61)] µg/ml, compared with control subjects [11.83 (± 2.85) µg/ml (P = 0.014)]. In multivariate analyses, serum pigment epithelium-derived factor concentration was associated with BMI (ß = 0.32, 0.007), homeostasis model assessment-insulin resistance (ß = 0.33, P = 0.01) and HDL (ß = -0.24, P = 0.05), after adjustment for age, gender and high-sensitivity C-reactive protein. In the niacin study, on-treatment HDL was an independent determinant of pigment epithelium-derived factor (ß = -0.439, P = 0.033), after adjusting for age, homeostasis model assessment-insulin resistance and treatment. Adipocytes treated with HDL were found to have reduced pigment epithelium-derived factor secretion [24.8% (50 µg/ml), 28.4% (100 µg/ml) HDL; P < 0.05)], compared with the control samples. CONCLUSION: Serum pigment epithelium-derived factor is positively associated with homeostasis model assessment-insulin resistance and negatively associated with HDL. Further studies are needed to understand the mechanism of low HDL and raised pigment epithelium-derived factor and to determine if they are causally related to the pathobiology of insulin resistance.


Subject(s)
Diabetes Mellitus, Type 2/blood , Eye Proteins/blood , Insulin Resistance , Lipoproteins, HDL/blood , Nerve Growth Factors/blood , Prediabetic State/blood , Serpins/blood , 3T3-L1 Cells , Adipocytes, White/metabolism , Adolescent , Adult , Aged , Animals , Body Mass Index , Cohort Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Eye Proteins/metabolism , Female , Follow-Up Studies , Humans , Lipoproteins, HDL/metabolism , Male , Mice , Middle Aged , Nerve Growth Factors/metabolism , Overweight/complications , Prediabetic State/complications , Prediabetic State/metabolism , Prospective Studies , Serpins/metabolism , Young Adult
19.
Protein Sci ; 21(7): 996-1005, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22544544

ABSTRACT

To examine the relationship between protein structural dynamics and measurable hydrogen exchange (HX) data, the detailed exchange behavior of most of the backbone amide hydrogens of Staphylococcal nuclease was compared with that of their neighbors, with their structural environment, and with other information. Results show that H-bonded hydrogens are protected from exchange, with HX rate effectively zero, even when they are directly adjacent to solvent. The transition to exchange competence requires a dynamic structural excursion that removes H-bond protection and allows exposure to solvent HX catalyst. The detailed data often make clear the nature of the dynamic excursion required. These range from whole molecule unfolding, through smaller cooperative unfolding reactions of secondary structural elements, and down to local fluctuations that involve as little as a single peptide group or side chain or water molecule. The particular motion that dominates the exchange of any hydrogen is the one that allows the fastest HX rate. The motion and the rate it produces are determined by surrounding structure and not by nearness to solvent or the strength of the protecting H-bond itself or its acceptor type (main chain, side chain, structurally bound water). Many of these motions occur over time scales that are appropriate for biochemical function.


Subject(s)
Hydrogen/chemistry , Micrococcal Nuclease/chemistry , Staphylococcus/enzymology , Hydrogen Bonding , Molecular Dynamics Simulation , Nuclear Magnetic Resonance, Biomolecular , Protein Folding , Protein Structure, Secondary , Staphylococcus/chemistry , Water/chemistry
20.
Protein Sci ; 21(7): 987-95, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22544567

ABSTRACT

To investigate the determinants of protein hydrogen exchange (HX), HX rates of most of the backbone amide hydrogens of Staphylococcal nuclease were measured by NMR methods. A modified analysis was used to improve accuracy for the faster hydrogens. HX rates of both near surface and well buried hydrogens are spread over more than 7 orders of magnitude. These results were compared with previous hypotheses for HX rate determination. Contrary to a common assumption, proximity to the surface of the native protein does not usually produce fast exchange. The slow HX rates for unprotected surface hydrogens are not well explained by local electrostatic field. The ability of buried hydrogens to exchange is not explained by a solvent penetration mechanism. The exchange rates of structurally protected hydrogens are not well predicted by algorithms that depend only on local interactions or only on transient unfolding reactions. These observations identify some of the present difficulties of HX rate prediction and suggest the need for returning to a detailed hydrogen by hydrogen analysis to examine the bases of structure-rate relationships, as described in the companion paper (Skinner et al., Protein Sci 2012;21:996-1005).


Subject(s)
Hydrogen/chemistry , Micrococcal Nuclease/chemistry , Models, Chemical , Staphylococcus/enzymology , Nuclear Magnetic Resonance, Biomolecular , Protein Folding , Staphylococcus/chemistry , Static Electricity
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