Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b
Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b
复制标题
DOI：
10.1016/s1097-2765(02)00525-7
复制
发表时间：
2002-06-01
期刊：
影响因子：
16
通讯作者：
Goldsmith, EJ
中科院分区：
文献类型：
--
作者：
Chang, CI;Xu, BE;Goldsmith, EJ
MAP激酶p38与底物MEF2a和激活酶MKK3b形成的含有Phi(A)-X-Phi(B)基序的多肽的络合物的结构已经被解决。这些多肽与该激酶C-末端结构域中的相同部位结合，该部位既在活性部位之外，又不同于先前在对接部位相互作用中所涉及的“CD”部位。对p38与对接位置相互作用的突变分析支持结晶学模型，并发现了对接凹槽上两个对结合至关重要的新残基。这两个多肽在多肽结合槽局部引起类似的大构象变化。这些多肽还会在活性部位引起意想不到的不同构象变化，以及磷酸化嘴唇的结构紊乱。
The structures of the MAP kinase p38 in complex with docking site peptides containing a phi(A)-X-phi(B) motif, derived from substrate MEF2A and activating enzyme MKK3b, have been solved. The peptides bind to the same site in the C-terminal domain of the kinase, which is both outside the active site and distinct from the "CD" domain previously implicated in docking site interactions. Mutational analysis on the interaction of p38 with the docking sites supports the crystallographic models and has uncovered two novel residues on the docking groove that are critical for binding. The two peptides induce similar large conformational changes local to the peptide binding groove. The peptides also induce unexpected and different conformational changes in the active site, as well as structural disorder in the phosphorylation lip.