Taylor P, Mikol V, Kallen J, Burkhard P, Walkinshaw M D
Structural Biochemistry Group, Department of Biochemistry, The University of Edinburgh, UK.
Biopolymers. 1996;40(5):585-92. doi: 10.1002/(sici)1097-0282(1996)40:5<585::aid-bip16>3.0.co;2-g.
Macrolide ligands that bind FK506 binding proteins and cyclosporins that a bind cyclophilins are chemically dissimilar but can share a number of structural and biological properties. Both families of ligands have very different conformations in the free state compared to those adopted when complexed with their binding protein. These transformations involve twisting from cis to trans about specific amide bonds, which result in significant changes in the hydrogen-bonding capabilities of the molecular surfaces. The three-dimensional structure of a new cyclosporin-like ligand (SDZ214 - 103) is described in the free crystalline state and bound to cyclophilin, and is shown to have a very different conformation from cyclosporin A in the free crystal, but a very similar conformation when bound to cyclophilin.
与FK506结合蛋白结合的大环内酯配体和与亲环蛋白结合的环孢菌素在化学上不同，但可具有一些结构和生物学特性。与结合蛋白复合时相比，这两类配体在游离状态下具有非常不同的构象。这些转变涉及特定酰胺键从顺式到反式的扭转，这导致分子表面氢键结合能力发生显著变化。描述了一种新的环孢菌素样配体（SDZ214 - 103）在游离晶体状态下以及与亲环蛋白结合时的三维结构，结果表明其在游离晶体中与环孢菌素A具有非常不同的构象，但与亲环蛋白结合时构象非常相似。
