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Tissue-nonspecific alkaline phosphatase (TNAP) from Homo sapiens and its membrane docking mechanism - a biophysical approach

Grant number: 13/26088-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2015
Effective date (End): October 31, 2015
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Antonio José da Costa Filho
Grantee:Assuero Faria Garcia
Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Alkaline phosphatases are enzymes that catalyze the hydrolysis of phosphomonoesters, thus producing phosphate and alcohol. These enzymes are dimers in solution and are found in the great majority of organisms. In humans, four alkaline phosphatases have been identified so far. Three of them are tissue-nonspecific alkaline phosphatases (TNAP) and can be expressed in any tissue in the body. In mammals, this enzyme is associated with a genetic disorder that can lead to different levels of failure of the bone mineralization (hypophosphatasia). The mechanisms used by TNAPs to permform their functions are still not completely understood, but it is believed that TNAPs somehow contribute to the increase of organic phosphate concentrations, promote bone mineralization, decreases concentration of extracellular phosphate, amongst others. TNAP is localized at the external part of the plasma membrane by means of a GPI (glycosylphosphatidylinositol) anchor. It is also frequently found associated with lipid rafts. Due to its biological relevance, TNAP has attracted attention of scientists from areas ranging from public health to basic Science, such as molecular biophysics. In this context, we propose in this project to use our expertise in the field of molecular biology and molecular biophysics to address the effects of lipid composition in the anchoring mechanism of TNAP and its natural mutants related to hypophosphatasia, as well as the effects of membrane models in the catalytic activity. To do so we will make use of a combined approach that will provide new insights about the TNAP structural features and its action mechanism, and it will be an important advance on basic Science and public health. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GARCIA, A. F.; SIMAO, A. M. S.; BOLEAN, M.; HOYLAERTS, M. F.; MILLAN, J. L.; CIANCAGLINI, P.; COSTA-FILHO, A. J. Effects of GPI-anchored TNAP on the dynamic structure of model membranes. Physical Chemistry Chemical Physics, v. 17, n. 39, p. 26295-26301, 2015. Web of Science Citations: 3.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.