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Science 10 May 1991:
Vol. 252. no. 5007, pp. 836 - 839
DOI: 10.1126/science.1709301
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Articles

Science, Vol 252, Issue 5007, 836-839
Copyright © 1991 by American Association for the Advancement of Science

articles

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

SW Michnick, MK Rosen, TJ Wandless, M Karplus, and SL Schreiber

Department of Chemistry, Harvard University, Cambridge, MA 02138.

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 beta-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.


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