The Bcl-2 family of proteins regulate programmed cell death (apoptosis) by an unknown mechanism. This process is a strictly regulated device for removing unnecessary, aged or damaged cells. Abnormal resistance to apoptosis causes malformations, autoimmune disease or cancer. In contrast, enhanced apoptotic decay of cells may play a role in both acute diseases and chronic pathologies. Naturally, there is a great interest in atomic structure of these proteins. A structure of human inhibitor of apoptosis, Bcl-XL, has been determined by both X-ray and NMR. No coordinates for a long flexible loop (residues 28-80) were determined, since no electron density and insufficient NOEs were observed for this fragment. Mutation studies suggest, however, that serine phosphorylation in the flexible loop region of Bcl-2 has a very important regulatory function. The program FANTOM is being used to model the structure of the flexible loop.
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