Kornev Alexandr P, Haste Nina M, Taylor Susan S, Eyck Lynn F Ten
San Diego Supercomputer Center, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17783-8. doi: 10.1073/pnas.0607656103. Epub 2006 Nov 9.
The surface comparison of different serine-threonine and tyrosine kinases reveals a set of 30 residues whose spatial positions are highly conserved. The comparison between active and inactive conformations identified the residues whose positions are the most sensitive to activation. Based on these results, we propose a model of protein kinase activation. This model explains how the presence of a phosphate group in the activation loop determines the position of the catalytically important aspartate in the Asp-Phe-Gly motif. According to the model, the most important feature of the activation is a "spine" formation that is dynamically assembled in all active kinases. The spine is comprised of four hydrophobic residues that we detected in a set of 23 eukaryotic and prokaryotic kinases. It spans the molecule and plays a coordinating role in activated kinases. The spine is disordered in the inactive kinases and can explain how stabilization of the whole molecule is achieved upon phosphorylation.
不同丝氨酸 - 苏氨酸激酶和酪氨酸激酶的表面比较揭示了一组30个残基，其空间位置高度保守。活性和非活性构象之间的比较确定了那些对激活最为敏感的残基位置。基于这些结果，我们提出了一种蛋白激酶激活模型。该模型解释了激活环中磷酸基团的存在如何决定Asp - Phe - Gly基序中催化重要的天冬氨酸的位置。根据该模型，激活的最重要特征是在所有活性激酶中动态组装形成的“脊柱”。脊柱由我们在一组23种真核和原核激酶中检测到的四个疏水残基组成。它跨越分子并在激活的激酶中起协调作用。脊柱在非活性激酶中是无序的，并且可以解释磷酸化后如何实现整个分子的稳定。
