Chao S H, Suzuki Y, Zysk J R, Cheung W Y
Mol Pharmacol. 1984 Jul;26(1):75-82.
The active form of calmodulin is a Ca2+ . calmodulin complex. The purpose of this investigation was to determine whether other metal cations substitute for Ca2+ to activate calmodulin. Binding of Ca2+ resulted in an altered conformation of calmodulin with an increased quantum yield in its tyrosine fluorescence. Qualitatively similar results were obtained with Zn2+, Mn2+, Cd2+, Hg2+, Sr2+, Pb2+, Tb3+, Sm3+, and La3+. The relative extents of fluorescence enhancement by these cations were related to their ionic radii: all cations with ionic radii close to Ca2+ (0.99 A) increased tyrosine fluorescence, whereas those with different ionic radii were not effective, or much less so. The change in calmodulin conformation by the cations was confirmed by its altered electrophoretic mobility on polyacrylamide gels. Cations that change the conformation of calmodulin allow it to stimulate phosphodiesterase. The relative extents of stimulation of phosphodiesterase by cations were also related to their ionic radii. Finally, the ability of metal cations to inhibit Ca2+ binding was similarly related to their ionic radii. In general, the closer the radius of a metal cation was to that of Ca2+, the more effective was the cation to substitute for Ca2+. The range of effective ionic radii was approximately 1 +/- 0.2 A. Calmodulin-stimulated phosphodiesterase activity by the cations was reversed by trifluoperazine, an antagonist of calmodulin.
钙调蛋白的活性形式是一种Ca2+·钙调蛋白复合物。本研究的目的是确定是否有其他金属阳离子能替代Ca2+来激活钙调蛋白。Ca2+的结合导致钙调蛋白构象改变，其酪氨酸荧光的量子产率增加。用Zn2+、Mn2+、Cd2+、Hg2+、Sr2+、Pb2+、Tb3+、Sm3+和La3+也得到了定性相似的结果。这些阳离子增强荧光的相对程度与其离子半径有关：所有离子半径接近Ca2+（0.99 Å）的阳离子都能增加酪氨酸荧光，而那些离子半径不同的阳离子则无效或效果差得多。钙调蛋白构象的改变通过其在聚丙烯酰胺凝胶上电泳迁移率的改变得到证实。能改变钙调蛋白构象的阳离子能使其刺激磷酸二酯酶。阳离子刺激磷酸二酯酶的相对程度也与其离子半径有关。最后，金属阳离子抑制Ca2+结合的能力同样与其离子半径有关。一般来说，金属阳离子的半径越接近Ca2+的半径，其替代Ca2+的效果就越好。有效离子半径范围约为1±0.2 Å。钙调蛋白刺激的阳离子磷酸二酯酶活性可被钙调蛋白拮抗剂三氟拉嗪逆转。
