Niefind K, Raaf J, Issinger O-G
Department für Chemie, Institut für Biochemie, Universität zu Köln, Zülpicher Strasse 47, 50674, Köln, Germany.
Cell Mol Life Sci. 2009 Jun;66(11-12):1800-16. doi: 10.1007/s00018-009-9149-8.
Within the last decade, 40 crystal structures corresponding to protein kinase CK2 (former name 'casein kinase 2'), to its catalytic subunit CK2alpha and to its regulatory subunit CK2beta were published. Together they provide a valuable, yet by far not complete basis to rationalize the biochemical features of the enzyme, such as its constitutive activity, acidophilic substrate specificity, dual-cosubstrate specificity and its heterotetrameric quarternary structure. Comprehensive sets of structural superimpositions reveal that both CK2alpha and CK2beta are relatively rigid molecules. In CK2beta the critical region of CK2alpha recruitment is pre-formed in the unbound state. In CK2alpha the activation segment - a key element of protein kinase regulation - adapts invariably the typical conformation of the active enzymes. Recent structures of human CK2alpha revealed a surprising plasticity in the ATP-binding region, suggesting an alternative mode of activity control.
在过去十年间，发表了40种与蛋白激酶CK2（原名“酪蛋白激酶2”）、其催化亚基CK2α及其调节亚基CK2β相对应的晶体结构。它们共同为解释该酶的生化特性提供了有价值但远未完整的基础，比如其组成型活性、嗜酸性底物特异性、双辅底物特异性及其异源四聚体四级结构。全面的结构叠加集表明，CK2α和CK2β都是相对刚性的分子。在CK2β中，CK2α招募的关键区域在未结合状态下预先形成。在CK2α中，激活片段——蛋白激酶调节的关键元件——始终采用活性酶的典型构象。人类CK2α的最新结构显示，ATP结合区域存在惊人的可塑性，提示了一种活性控制的替代模式。
