This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Structural genomics has reached an era where focus has been shifted to making more substantial contribution to the biological community. Our group operates the x-ray crystallography facility of two PSI-II centers ? the Integrated Center for Structure and Function Innovation (ISFI) and the TB Structural Genomics Consortium (TBSGC). The two centers focus on develop technologies to solve crystal structures of important but difficult targets (ISFI), and to solve those of important drug targets of Mycobacterium tuberculosis. Because of the difficulty of the targets, most of the crystals are difficult to obtain and often very small. Well managed and intense synchrotron sources optimized for protein crystallography are usually the only hope in conducting effective diffraction experiments. Characterizing and solving the crystal structures of these proteins of biomedical importance will bring substantial impact to the biological community.