Lipid recognition propensities of amino acids in membrane proteins from atomic resolution data

Background

Protein-lipid interactions play essential roles in the conformational stability and biological functions of membrane proteins. However, few of the previous computational studies have taken into account the atomic details of protein-lipid interactions explicitly.

Results

To gain an insight into the molecular mechanisms of the recognition of lipid molecules by membrane proteins, we investigated amino acid propensities in membrane proteins for interacting with the head and tail groups of lipid molecules. We observed a common pattern of lipid tail-amino acid interactions in two different data sources, crystal structures and molecular dynamics simulations. These interactions are largely explained by general lipophilicity, whereas the preferences for lipid head groups vary among individual proteins. We also found that membrane and water-soluble proteins utilize essentially an identical set of amino acids for interacting with lipid head and tail groups.

Conclusions

We showed that the lipophilicity of amino acid residues determines the amino acid preferences for lipid tail groups in both membrane and water-soluble proteins, suggesting that tightly-bound lipid molecules and lipids in the annular shell interact with membrane proteins in a similar manner. In contrast, interactions between lipid head groups and amino acids showed a more variable pattern, apparently constrained by each protein's specific molecular function.     

Biotribology of articular cartilage--a review of the recent advances

A brief review of the advances in the biotribology of articular cartilage in the last decade or so are presented. The review is limited to experimental friction and wear studies involving articular cartilage. The importance of developing in vitro models as tools not only to understand the cartilage tribological characteristics, but to evaluate current and future cartilage substitution and treatment therapies is discussed.     

Diltiazem-induced photodistributed hyperpigmentation

Diltiazem is a calcium-channel antagonist commonly prescribed in the treatment of cardiovascular disease. Although an extensive spectrum of cutaneous reactions to diltiazem has been described, only two published reports of hyperpigmentation induced by diltiazem are known. We report the cases of a 71-year-old black male and a 49-year-old Hispanic male, who both presented with characteristic hyperpigmentation on sun-exposed areas after taking an extended-release form of diltiazem hydrochloride (Tiazac).     

Triphasic Randomized Clinical Trial: comparative frequency of intermenstrual bleeding

Oral contraceptives have the highest theoretic efficacy of all reversible forms of contraception, yet in practice they have an actual failure rate equivalent to that of some barrier methods. The efficacy of oral contraceptives depends primarily on patient compliance. So-called "nuisance" side effects, such as intermenstrual bleeding (breakthrough bleeding or spotting), play a major role in their discontinuation. The Triphasic Randomized Clinical Trial compared the incidence of these side effects in three groups of subjects taking NET (A) (Ortho-Novum 7/7/7), LNG (Tri-Levlen), or NET (B) (Tri-Norinyl). Subjects taking NET (A) had the highest incidence of intermenstrual bleeding (63%) followed by NET (B) (44%) and LNG (33%). Only the difference between NET (A) and LNG attained statistical significance (p less than 0.030). Control subjects had no breakthrough bleeding and a 4% incidence of spotting. Further research is warranted to establish the cause of the disparity in the incidence of intermenstrual bleeding among patient groups assigned to the three oral triphasic contraceptives.     

Inhibition of gonadotropin-releasing hormone receptors in rat anterior pituitary monolayer cell cultures by danazol

To study possible cellular antigonadotropic effects of danazol, monolayer cultures of anterior pituitary cells from immature female rats were treated with danazol. Measurements of luteinizing hormone release in response to 10(-8) mol/L gonadotropin-releasing hormone challenge and iodine 125-labeled gonadotropin-releasing hormone binding activity were done after exposure to increasing concentrations of danazol and for increasing lengths of time. It was found that luteinizing hormone secreted by pituitary cells in response to gonadotropin-releasing hormone was inhibited after danazol treatment in a dose- and time-dependent manner when compared to controls. Also, a 45% decrease in gonadotropin-releasing hormone receptor binding capacity was observed in pituitary cells cultured in the presence of increasing concentrations of danazol in the range of 10(-8) to 10(-4) mol/L when compared to controls. Furthermore, exposure to danazol for 25 to 96 hours caused a marked decrease in gonadotropin-releasing hormone binding activity (p less than 0.005). Under these experimental conditions danazol treatment decreased the pituitary receptors for gonadotropin-releasing hormone in a dose- and time-dependent manner. Scatchard analysis of saturation curves for the binding of gonadotropin-releasing hormone to cellular gonadotropin-releasing hormone receptors indicated that the observed decrease in gonadotropin-releasing hormone binding in the danazol-treated group was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. It is therefore concluded that the antigonadotropic activity of danazol appears to be related to a decrease in gonadotropin-releasing hormone receptors in the pituitary.     

Pigmented vulvar macules as a presenting feature of the Carney complex.

A 27‐year‐old woman was referred by her gynecologist for asymptomatic pigmented vulvar lesions first noted 2 years previously. Medical history was significant for a personal history of atrial myxoma, diagnosed due to a systolic murmur, along with a family (maternal) history of atrial myxoma. The patient also reported irregular menses, increasing and darkening of body and facial hair, and an increase in shoe size. Physical examination revealed multiple 2‐5 mm dark brown to black macules on the labia majora and minora. ( Fig. 1 ) Faint scattered light brown macules were noted on the chest and face. A 2‐mm brown scleral macule was present adjacent to the iris, and scattered small pigmented macules were present on the vermilion border of the lips. A 4‐mm blue‐black papule was found on the upper back, and several firm, 2 mm flesh‐colored papules were found on the abdomen and thigh. Hypertrichosis of both forearms was present, and enlargement of the jaw and hands was noted.

Figure 1 Open in figure viewer PowerPoint Multiple dark brown to black macules on the labia majora and minora     

A rapid-room temperature synthesis of α-cyanoacrylates, α-cyanoacrylonitriles and 4H-pyrans using water extract of pomegranate ash as catalytic media

In this article we report a sustainable and rapid-room temperature synthesis of α-cyanoacrylonitriles, α-cyanoacrylates, and 4H-pyrans via the condensation of active methylene compounds with aldehydes, and a three-component reaction of 1,3-dicarbonyl compounds/4-hydroxycoumarins, active methylene compounds and acetylene dicarboxylates in water extract of pomegranate ash (WEPA). The agro-waste-derived WEPA acts both as catalyst and aqueous reaction medium. The products of this process were separated by simple filtration and purified by recrystallization. This protocol did not require organic solvent-based work-up and column chromatography-assisted purifications. The use of renewable catalytic media, good reusability of catalyst, ease of handling, ambient and depleting resources-based catalyst free conditions, avoid of volatile organic solvents throughout the process, excellent product yields, and actual usage of waste are the highlights of this process.