DRUG-BINDING BY CALMODULIN - CRYSTAL-STRUCTURE OF A CALMODULIN TRIFLUOPERAZINE COMPLEX
DRUG-BINDING BY CALMODULIN - CRYSTAL-STRUCTURE OF A CALMODULIN TRIFLUOPERAZINE COMPLEX
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DOI：
10.1021/bi00255a006
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发表时间：
1994-12-27
期刊：
影响因子：
2.9
通讯作者：
WALTER, MR
中科院分区：
文献类型：
--
作者：
COOK, WJ;WALTER, LJ;WALTER, MR
与三氟拉嗪 (TFP) 结合的钙调蛋白 (CaM) 的晶体结构已被测定并精炼至分辨率为 2.45 埃。只有一个 TFP 与 CaM 结合，但这足以引起中央 α 螺旋的扭曲以及 N 端和 C 端结构域的并置，类似于 CaM 多肽复合物中所见的情况。该药物与 CaM C 端结构域中的残基广泛接触，但与 N 端结构域中的一个残基仅有少量接触。该结构表明，与 C 端结构域结合的底物足以引起钙调蛋白的构象变化，从而导致其靶标的激活。
The crystal structure of calmodulin (CaM) bound to trifluoperazine (TFP) has been determined and refined to a resolution of 2.45 Angstrom. Only one TFP is bound to CaM, but that is sufficient to cause distortion of the central a-helix and juxtaposition of the N- and C-terminal domains similar to that seen in CaM-polypeptide complexes. The drug makes extensive contacts with residues in the C-terminal domain of CaM but only a few contacts with one residue in the N-terminal domain. The structure suggests that substrate binding to the C-terminal domain is sufficient to cause the conformational changes in calmodulin that lead to activation of its targets.