Michnick S W, Rosen M K, Wandless T J, Karplus M, Schreiber S L
Department of Chemistry, Harvard University, Cambridge, MA 02138.
Science. 1991 May 10;252(5007):836-9. doi: 10.1126/science.1709301.
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.
免疫亲和素与免疫抑制配体结合时，似乎会抑制导致胞吐作用和转录的信号转导途径。其中之一，即人FK506和雷帕霉素结合蛋白（FKBP）的溶液结构已通过核磁共振（NMR）确定。FKBP具有一种以前未观察到的反平行β-折叠拓扑结构，这种结构导致了一种新的环交叉，并产生了一个由保守的芳香族残基阵列排列而成的大腔；这个腔作为肽基脯氨酰顺反异构酶活性位点和药物结合口袋。还有其他重要的结构特征（如一个突出的带正电荷的环和一个明显灵活的环）可能参与FKBP的生物活性。
