title: Functional diversity and pharmacological profiles of the FKBPs and their complexes with small natural ligands.
abstract: From 5 to 12 FK506-binding proteins (FKBPs) are encoded in the genomes of disparate marine organisms, which appeared at the dawn of evolutionary events giving rise to primordial multicellular organisms with elaborated internal body plan. Fifteen FKBPs, several FKBP-like proteins and some splicing variants of them are expressed in humans. Human FKBP12 and some of its paralogues bind to different macrocyclic antibiotics such as FK506 or rapamycin and their derivatives. FKBP12/(macrocyclic antibiotic) complexes induce diverse pharmacological activities such as immunosuppression in humans, anticancerous actions and as sustainers of quiescence in certain organisms. Since the FKBPs bind to various assemblies of proteins and other intracellular components, their complexes with the immunosuppressive drugs may differentially perturb miscellaneous cellular functions. Sequence-structure relationships and pharmacological profiles of diverse FKBPs and their involvement in crucial intracellular signalization pathways and modulation of cryptic intercellular communication networks were discussed.
authors.affiliation: Commissariat à l'Energie Atomique, Direction des Sciences du Vivant, Institut de Biologie et de Technologies de Saclay, Service d'Ingénierie Moléculaire des Protéines, Bat. 152, 91191, Gif-sur-Yvette Cedex, France. galat@dsvidf.cea.fr
authors.forename: Andrzej
authors.initials: A
authors.lastname: Galat
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002450:Cell Communication; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D008024:Ligands; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D020123:Sirolimus / Q000627:therapeutic use; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D008024:Ligands; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus