菌素轻链激酶的胃内调节的结构基础
D R Knighton1, R B Pearson, J M Sowadski
1Department of Chemistry, University of California San Diego, La Jolla 92093-0654.
概括
光滑肌肉髓素轻链激酶 (smMLCK) 结构是使用相关激酶建模的. 这揭示了一个合理的分子内机制调节smMLCK活动.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 光滑肌肉髓轻链激酶 (smMLCK) 调节肌肉收缩.
- smMLCK的催化核心和调节机制尚未完全理解.
研究的目的:
- 为了建模smMLCK的催化核心.
- 通过其伪基质序列来研究smMLCK调节的结构基础.
主要方法:
- 使用循环AMP依赖蛋白激酶催化子单元 (cAPK) 的晶体坐标进行同质模型.
- 一个伪基质抑制剂的建模 (PKI(5-24)).
主要成果:
- smMLCK的催化核心可以在cAPK结构中建模,这表明保留了二次结构元素.
- 活动部位模型与已知的基质识别要求一致.
- smMLCK的伪基质序列合理地占据了基质结合部位,支持了内抑制模型.
结论:
- 在结构上支持smMLCK调节的内抑制模型.
- 这个模型解释了smMLCK在没有Ca(2+) -calmodulin的情况下是如何被抑制的.
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