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Comparative biochemical analysis of three members of the Schistosoma mansoni TAL family: Differences in ion and drug binding properties.

ABSTRACT: The tegumental allergen-like (TAL) proteins from Schistosoma mansoni are part of a family of calcium binding proteins found only in parasitic flatworms. These proteins have attracted interest as potential drug or vaccine targets, yet comparatively little is known about their biochemistry. Here, we compared the biochemical properties of three members of this family: SmTAL1 (Sm22.6), SmTAL2 (Sm21.7) and SmTAL3 (Sm20.8). Molecular modelling suggested that, despite similarities in domain organisation, there are differences in the three proteins' structures. SmTAL1 was predicted to have two functional calcium binding sites and SmTAL2 was predicted to have one. Despite the presence of two EF-hand-like structures in SmTAL3, neither was predicted to be functional. These predictions were confirmed by native gel electrophoresis, intrinsic fluorescence and differential scanning fluorimetry: both SmTAL1 and SmTAL2 are able to bind calcium ions reversibly, but SmTAL3 is not. SmTAL1 is also able to interact with manganese, strontium, iron(II) and nickel ions. SmTAL2 has a different ion binding profile interacting with cadmium, manganese, magnesium, strontium and barium ions in addition to calcium. All three proteins form dimers and, in contrast to some Fasciola hepatica proteins from the same family; dimerization is not affected by calcium ions. SmTAL1 interacts with the anti-schistosomal drug praziquantel and the calmodulin antagonists trifluoperazine, chlorpromazine and W7. SmTAL2 interacts only with W7. SmTAL3 interacts with the aforementioned calmodulin antagonists and thiamylal, but not praziquantel. Overall, these data suggest that the proteins have different biochemical properties and thus, most likely, different in vivo functions.

SUBMITTER: Thomas CM

PROVIDER: S-EPMC4300400 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Comparative biochemical analysis of three members of the Schistosoma mansoni TAL family: Differences in ion and drug binding properties.

Thomas Charlotte M CM Fitzsimmons Colin M CM Dunne David W DW Timson David J DJ

Biochimie 20141105

The tegumental allergen-like (TAL) proteins from Schistosoma mansoni are part of a family of calcium binding proteins found only in parasitic flatworms. These proteins have attracted interest as potential drug or vaccine targets, yet comparatively little is known about their biochemistry. Here, we compared the biochemical properties of three members of this family: SmTAL1 (Sm22.6), SmTAL2 (Sm21.7) and SmTAL3 (Sm20.8). Molecular modelling suggested that, despite similarities in domain organisatio ...[more]

PMID: 25447146

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Project description:BackgroundSchistosomes are blood dwelling parasites that affect more than 260 million people globally, and over 800 million people are at risk of infection in 74 countries. It causes acute and chronic debilitating diseases. The parasite is reported to alter the hematological and biochemical parameters in humans. Therefore, this study was aimed to evaluate the hematological and biochemical changes in S. mansoni infected adult patients compared to apparently healthy controls.MethodsA comparative cross-sectional study was conducted at Haik Primary Hospital from February to April 2021. One hundred and eighty study participants consisting of 90 S. mansoni infected patients and 90 apparently healthy controls were recruited using systematic random sampling method. Socio-demographic characteristics and other variables were collected using questionnaires. Stool sample was examined microscopically to detect S. mansoni infection using direct wet mount and Kato Katz technique. In apparently healthy controls, S. mansoni infection was rule out using direct wet mount and Kato Katz technique. Moreover, the intensity of S. mansoni infection was assessed using Kato Katz technique. Blood sample was collected from each study participant to determine the hematological and biochemical profiles. Data were entered in to Epi Data version 3.1 and analyzed using SPSS version 26.0 software. Kolmogorov-Smirnov and Shapiro Wilk normality tests were done to assess the distribution of continuous variables. The Mann-Whitney U test and Kruskal Wallis H test was done to compare the differences among nonnormally distributed variables between S. mansoni infected patients and healthy controls. P-values <0.05 at 95%CI were considered as statistically significant.ResultThe mean age (SD) of S. mansoni infected patients and apparently healthy controls was 30.33 (±12.26) and 31.2 (±12.85) years old, respectively. The prevalence of anemia, and thrombocytopenia among S. mansoni infected patients were 23.3% and 26.7%, respectively. Erythrocytic sedimentation rate (ESR) was significantly elevated among S. mansoni infected patients than apparently healthy controls. The median white blood cell count, red blood cell count, red blood cell indices, and platelet indices were significantly lower among S. mansoni infected patients compared to apparently healthy controls (P<0.05). On the other hand, the median eosinophil count was significantly elevated among S. mansoni infected patients compared to apparently healthy controls (P<0.05). This study also showed significantly elevated values of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and direct bilirubin and lower albumin, total cholesterol and triglycerides among S. mansoni infected patients compared to apparently healthy controls. Kruskal Wallis H test showed a significant difference in the median of most hematological and biochemical parameters between moderate and heavy intensity of infection with light intensity of infection and apparently healthy controls.ConclusionThe findings of this study showed significantly altered hematological values and liver function tests among S. mansoni infected patients compared to apparently healthy controls. Therefore, screening of S. mansoni infected patients for various hematological and biochemical parameters and providing treatment to the underlying abnormalities is very crucial to avoid schistosomiasis associated morbidity and mortality.

Dataset Information

Comparative biochemical analysis of three members of the Schistosoma mansoni TAL family: Differences in ion and drug binding properties.

Publications

Comparative biochemical analysis of three members of the Schistosoma mansoni TAL family: Differences in ion and drug binding properties.

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