Cyclic nucleotide selectivity of protein kinase G isozymes.
Cyclic nucleotide selectivity of protein kinase G isozymes.
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蛋白激酶 G 同工酶的环核苷酸选择性。
DOI：
10.1002/pro.4008
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Sharma,Rajesh
中科院分区：
文献类型：
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作者：
Kim,Choel;Sharma,Rajesh
环鸟苷(CGMP)依赖的蛋白激酶(PKG)的C端催化(C)结构域的内在活性被与N端调节(R)结构域相互作用所抑制。CGMP与R结构域中的环核苷酸结合(CNB)结构域的选择性结合破坏了抑制的R-C相互作用，导致C结构域的释放和激活。哺乳动物和疟原虫PKG CNB结构域的亲和力测量显示出不同程度的环核苷酸亲和力和选择性；与C结构域相邻的CNB结构域具有更高的cGMP选择性，因此对cGMP依赖的激活至关重要。在环核苷酸存在和不存在的情况下，分离的CNB结构域的晶体结构揭示了同工酶特异的接触，解释了伴随CNB的环核苷酸选择性和构象变化。串联CNB结构域的晶体结构识别了两种类型的CNB介导的二聚体接触，这表明cGMP驱动的结构域界面的重组包括大的构象变化。在这里，我们综述了现有的PKG CNB结构域的结构和功能信息，以进一步加深我们对cGMP介导的PKG同工酶的调控和激活的理解。
The intrinsic activity of the C‐terminal catalytic (C) domain of cyclic guanosine monophosphate (cGMP)‐dependent protein kinases (PKG) is inhibited by interactions with the N‐terminal regulatory (R) domain. Selective binding of cGMP to cyclic nucleotide binding (CNB) domains within the R‐domain disrupts the inhibitory R–C interaction, leading to the release and activation of the C‐domain. Affinity measurements of mammalian and plasmodium PKG CNB domains reveal different degrees of cyclic nucleotide affinity and selectivity; the CNB domains adjacent to the C‐domain are more cGMP selective and therefore critical for cGMP‐dependent activation. Crystal structures of isolated CNB domains in the presence and absence of cyclic nucleotides reveal isozyme‐specific contacts that explain cyclic nucleotide selectivity and conformational changes that accompany CNB. Crystal structures of tandem CNB domains identify two types of CNB‐mediated dimeric contacts that indicate cGMP‐driven reorganization of domain–domain interfaces that include large conformational changes. Here, we review the available structural and functional information of PKG CNB domains that further advance our understanding of cGMP mediated regulation and activation of PKG isozymes.