Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin

Stephen W. Michnick, Michael K. Rosen, Thomas J. Wandless, Martin Karplus, Stuart L. Schreiber

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Abstract

Immunophilins, when complexed to immunosuppressive ligands, appear to inhibit signal transduction pathways that result in exocytosis and transcription. The solution structure of one of these, the human FK506 and rapamycin binding protein (FKBP), has been determined by nuclear magnetic resonance (NMR). FKBP has a previously unobserved antiparallel β-sheet folding topology that results in a novel loop crossing and produces a large cavity lined by a conserved array of aromatic residues; this cavity serves as the rotamase active site and drug-binding pocket. There are other significant structural features (such as a protruding positively charged loop and an apparently flexible loop) that may be involved in the biological activity of FKBP.

Original languageEnglish (US)
Pages (from-to)836-839
Number of pages4
JournalScience
Volume252
Issue number5007
DOIs
StatePublished - May 10 1991

ASJC Scopus subject areas

  • General

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    Michnick, S. W., Rosen, M. K., Wandless, T. J., Karplus, M., & Schreiber, S. L. (1991). Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin. Science, 252(5007), 836-839. https://doi.org/10.1126/science.1709301