title: Crystal structure of the FK506 binding domain of human FKBP25 in complex with FK506.
abstract: Human FKBP25 (hFKBP25) is a nuclear immunophilin and interacts with several nuclear proteins, hence involving in many nuclear events. Similar to other FKBPs, FK506 binding domain (FKBD) of hFKBP25 also binds to immunosuppressive drugs such as rapamycin and FK506, albeit with a lower affinity for the latter. The molecular basis underlying this difference in affinity could not be addressed due to the lack of the crystal structure of hFKBD25 in complex with FK506. Here, we report the crystal structure of hFKBD25 in complex with FK506 determined at 1.8 Å resolution and its comparison with the hFKBD25-rapamycin complex, bringing out the microheterogeneity in the mode of interaction of these drugs, which could possibly explain the lower affinity for FK506.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
authors.forename: Ajit
authors.initials: A
authors.lastname: Prakash
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
authors.forename: Sreekanth
authors.initials: S
authors.lastname: Rajan
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.|Department of Genetic Engineering, College of Life Sciences, Kyung Hee University Yongin-si, Gyeonggi-do, 446-701, Republic of Korea.
authors.forename: Ho Sup
authors.initials: HS
authors.lastname: Yoon
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D020123:Sirolimus / Q000378:metabolism; D013379:Substrate Specificity; D016559:Tacrolimus / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C074856:FKBP3 protein, human; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus; D016559:Tacrolimus
keywords: FK506; FKBD25; FKBP; FKBP25; crystal structure; immunophilin; inhibitor