X-RAY STRUCTURE OF CALCINEURIN INHIBITED BY THE IMMUNOPHILIN IMMUNOSUPPRESSANT FKBP12-FK506 COMPLEX
X-RAY STRUCTURE OF CALCINEURIN INHIBITED BY THE IMMUNOPHILIN IMMUNOSUPPRESSANT FKBP12-FK506 COMPLEX
复制标题
DOI：
10.1016/0092-8674(95)90439-5
复制
发表时间：
1995-08-11
期刊：
影响因子：
64.5
通讯作者：
NAVIA, MA
中科院分区：
文献类型：
--
作者：
GRIFFITH, JP;KIM, JL;NAVIA, MA
钙调磷酸酶A片段、钙调磷酸酶B、FKBP 12和免疫抑制剂药物FK 506（也称为他克莫司）的三元复合物的X射线结构已在2.5埃分辨率下测定，提供了FK 506如何在原子水平上起作用的描述。在该结构中，FKBP 12-FK 506二元复合物不接触钙调神经磷酸酶A上的磷酸酶活性位点，该位点被移除超过10埃。相反，FKBP 12-FK 506的位置使得它可以通过物理阻碍其大分子底物接近活性位点来抑制其去磷酸化。这里描述的三元复合物代表了Ser/Thr蛋白磷酸酶的三维结构，并为理解FKBP 12-FK 506对钙调磷酸酶的抑制作用提供了结构基础。
The X-ray structure of the ternary complex of a calcineurin A fragment, calcineurin B, FKBP12, and the immunosuppressant drug FK506 (also known as tacrolimus) has been determined at 2.5 Angstrom resolution, providing a description of how FK506 functions at the atomic level. In the structure, the FKBP12-FK506 binary complex does not contact the phosphatase active site on calcineurin A that is more than 10 Angstrom removed. Instead, FKBP12-FK506 is so positioned that it can inhibit the dephosphorylation of its macromolecular substrates by physically hindering their approach to the active site. The ternary complex described here represents the three-dimensional structure of a Ser/Thr protein phosphatase and provides a structural basis for understanding calcineurin inhibition by FKBP12-FK506.