Relationship between structure and function of alpha-fetoprotein: conformation changes and biological activity

   


1. Russian State Medical University
2. 2M. V. Lomonosov Moscow State University
Type: Review
PubMed Id: 15945348
Year: 2005 vol: 51  issue:2  pages: 127-151
Abstract: Alpha-fetoprotein (AFP) is the major mammalian fetal protein and the recognized tumor marker. This review summarizes data on structure and function of AFP with emphasis on human AFP, which is intensively investigated. During the last decade multiple functionally important sites of human AFP have been revealed or predicted by searching of similarity between primary structures of AFP and other proteins or their DNA sequences. A number of peptides were obtained by limited proteolysis of AFP or synthesized using solid phase chemistry. Study of biological (physiological) activities of these peptides allows determining biologically active sites of alpha-fetoprotein and constructing its structural and functional map. Biomodulating properties of these peptides make them a potential basis for design of drugs for different purposes including using in anticancer therapy. Conformational changes in AFP molecule have been intensively studies for the last few years and sufficient conformational mobility of AFP with the ability to form molten globule form (MGF) despite its stability in solution has been demonstrated. Native Molecule of AFP may contain cryptic biologically active sites, which are not available for ligand binding. These sites become open and available for interaction after changes in conformation of AFP molecule. Study of conformational changes of AFP under different conditions allows understanding molecular mechanism of its functioning. This review describes and analyses data obtained, mainly, during the last few years on study of conformational states of alpha-fetoprotein and relationship between conformational changes of AFP and its biological activity. Biochemical, biophysical and functional characteristics of some well-studied peptide fragments of AFP and their structural and functional mapping are presented.
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Reference: Moldogazieva N.T., Terentiev A.A., Shaitan K.V., Relationship between structure and function of alpha-fetoprotein: conformation changes and biological activity, Biomeditsinskaya khimiya, 2005, vol: 51(2), 127-151.
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