FKBP公司
异构酶
化学
肽基脯氨酰异构酶
立体化学
氢键
结晶学
构象变化
生物物理学
生物化学
生物
酶
分子
有机化学
作者
Gregory D. Van Duyne,Robert F. Standaert,P. Andrew Karplus,Stuart L. Schreiber,Jon Clardy
标识
DOI:10.1006/jmbi.1993.1012
摘要
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 β-sheet wrapping around a short α-helix with an overall conical shape. Both FK506 and rapamycin bind in the cavity defined by the β-sheet, α-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 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.
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