A structural biology laboratory network for the study of the 3D structures of proteins

Abstract

We envisage finding the structures of proteins which: I) have potential of playing a functional role in the induction and/or sustenance of malignant phenotypes in humans; II) are functionally important in plants and bacteria. For some of these proteins, attempts will be made to determine structures that may reveal new folds; III) exhibit high potential of having its structure determined by synchrotron radiation protein crystallography or multinuclear multidimensional high-resolution nuclear magnetic resonance spectroscopy (NMR). The choice of these proteins will be mainly based on the results of the F APESP Genomics Programs such as Xylella fastidiosa, Xanthomonas citri, Sugar Cane EST and the FAPESP/LICR Human Cancer. These Programs have produced an enormous amount of information, which need to be exploited from a structural and functional point of view. The knowledge of the structures of these proteins would disclose an attractively practical output, the rational design of inhibitors of the proteins, i.e. potential anti-cancer drugs in the case of the FAPESP/LICR Human Cancer project or herbicides/pesticides in the other cases. In parallel, we are also proposing to organize the Sao Paulo State Laboratory Network for Structural Biology, aimed at increasing the throughput of proteins to be analyzed and to expand the number of groups, in the State of Sao Paulo, involved in the area of Structural Biology. The F APESP genome programs have been important to increase significantly the number of laboratories with expertise in DNA sequencing and annotation. A further development in molecular biology involves increasing capabilities in protein structure determination, which, in turn, requires expertise in protein expression and purification. All these aspects are central to the present project. The creation of a network of laboratories is critical for the accomplishment of these goals. In addition, we hope that the laboratories that will be part of the network will be seeking to develop their interest in the study of the structural aspects of proteins. Thus, it is expected that they may work further down the project pipeline attempting either to crystallize proteins and collect diffraction data and/or to study the proteins in solution by means of NMR spectroscopy; with the final aim of solving their 3D structure(s). (AU)