Zhang G, Kazanietz M G, Blumberg P M, Hurley J H
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0580, USA.
Cell. 1995 Jun 16;81(6):917-24. doi: 10.1016/0092-8674(95)90011-x.
Protein kinase Cs (PKCs) are a ubiquitous family of regulatory enzymes that associate with membranes and are activated by diacylglycerol or tumor-promoting agonists such as phorbol esters. The structure of the second activator-binding domain of PKC delta has been determined in complex with phorbol 13-acetate, which binds in a groove between two pulled-apart beta strands at the tip of the domain. The C3, C4, and C20 phorbol oxygens form hydrogen bonds with main-chain groups whose orientation is controlled by a set of highly conserved residues. Phorbol binding caps the groove and forms a contiguous hydrophobic surface covering one-third of the domain, explaining how the activator promotes insertion of PKC into membranes.
蛋白激酶C（PKCs）是一类普遍存在的调节酶家族，它们与细胞膜结合，并可被二酰基甘油或肿瘤促进剂（如佛波酯）激活。已确定PKCδ的第二个激活剂结合结构域与佛波醇13-乙酸酯形成复合物的结构，佛波醇13-乙酸酯结合在该结构域顶端两条拉开的β链之间的凹槽中。佛波醇的C3、C4和C20氧原子与主链基团形成氢键，主链基团的取向由一组高度保守的残基控制。佛波醇的结合封闭了凹槽，并形成了一个覆盖该结构域三分之一的连续疏水表面，这解释了激活剂如何促进PKC插入细胞膜。
