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Structure of FKBP12.6 in complex with rapamycin
C C Deivanayagam1, M Carson, A Thotakura
1Center for Macromolecular Crystallography, School of Optometry, 250 BHSB, 1918 University Boulevard, Birmingham, AL 35294--0005, USA.
Abstract:
FKBP12.6 is a novel isoform of FKBP12, which selectively binds to the cardiac ryanodine receptor (RyR2). The crystal structure of FKBP12.6 in complex with rapamycin has now been determined at 2.0 A resolution. The structures of FKBP12.6 and FKBP12 are nearly identical, except for a displacement observed in the helical region of FKBP12.6 toward the hydrophobic pocket. This displacement was not predicted by homology modeling studies. Analyses of the residues that are likely to confer the RyR2-binding specificity are presented.