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Atomic structures of the human immunophilin FKBP-12 complexes with FK506 and rapamycin.
Department of Chemistry, Cornell University Ithaca, NY 14853-1301.
High resolution structures for the complexes formed by the immunosuppressive agents FK506 and rapamycin with the human immunophilin FKBP-12 have been determined by X-ray diffraction. FKBP-12 has a novel fold comprised of a five-stranded beta-sheet wrapping around a short alpha-helix with an overall conical shape. Both FK506 and rapamycin bind in the cavity defined by the beta-sheet, alpha-helix and three loops. Both FK506 and rapamycin bind in similar fashions with a set of hydrogen bonds and an unusual carbonyl binding pocket. Bound FK506 has a different conformation than free (crystalline) FK506 while rapamycin's bound conformation is virtually identical to that of unbound rapamycin. FKBP-12 is a peptidyl-prolyl isomerase (PPIase), and the structures of the complexes suggest ways in which this catalytic activity could operate. The different complexes are active in suppressing different steps of T cell activation, an activity seemingly unconnected with the PPIase activity.
PMID: 7678431 [PubMed - indexed for MEDLINE]
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Structural and functional analysis of AsbF: origin of the stealth 3,4-dihydroxybenzoic acid subunit for petrobactin biosynthesis.
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[Proc Natl Acad Sci U S A. 2008]
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[Proc Natl Acad Sci U S A. 2008]
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Patient Drug Information
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Tacrolimus (Prograf® )
Tacrolimus is used along with other medications to prevent rejection (attack of a transplanted organ by the immune system of a person receiving the organ) in people who have received kidney, liver, or heart transplants. ...
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Sirolimus (Rapamune® )
Sirolimus is used in combination with other medications to prevent rejection of kidney transplants. Sirolimus is in a class of medications called immunosuppressants. It works by suppressing the body's immune system.