Ligand preference and orientation in b- and c-type heme-binding proteins.
Ligand preference and orientation in b- and c-type heme-binding proteins.
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DOI：
10.1002/prot.22097
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发表时间：
2008-11-15
影响因子：
2.9
通讯作者：
Gunner, M. R.
中科院分区：
文献类型：
--
作者：
Fufezan, Christian;Zhang, Jun;Gunner, M. R.
血红素常被掺入设计好的蛋白质中。血红素配体类型及其取向的重要性仍然是一个有争议的问题。本研究使用非冗余（87个结构）和冗余（1503个结构）结构对血红素配体和配体取向进行了研究，以比较和对比天然b型和c型血红素结合蛋白的设计特征。组氨酸是最常见的配体。b型和c型血红素之间的连接基序的显著差异是c型血红素结合基序中His-Met的发生率较高（16.4%比1.4%），b型血红素结合基序中可交换小分子的发生率较高（67.6%比9.9%）。组氨酸配体是c型CXXCH血红素结合基序的一部分，具有明显的不对称取向分布。它们要么指向丙酸血红素，要么指向NA和NB血红素氮。分子力学计算表明，这种不对称是由于血红素和蛋白质之间的共价连接的键约束。相比之下，b型血红素组氨酸配体的取向分布均匀，没有偏好。观察到组氨酸血红素配体的取向显示血红素丙酸酯和配体之间的静电相互作用没有主导影响。此外，在his血红素中的配体通常是相互垂直的，而不是相互平行的。这些相关性支持对配体的能量限制，可以用于设计蛋白质。
Hemes are often incorporated into designed proteins. The importance of the heme ligand type and its orientation is still a matter of debate. Here, heme ligands and ligand orientation were investigated using a nonredundant (87 structures) and a redundant (1503 structures) set of structures to compare and contrast design features of natural b- and c-type heme-binding proteins. Histidine is the most common ligand. Marked differences in ligation motifs between b- and c-type hemes are higher occurrence of His-Met in c-type heme binding motifs (16.4% vs. 1.4%) and higher occurrence of exchangeable, small molecules in b-type heme binding motifs (67.6% vs. 9.9%). Histidine ligands that are part of the c-type CXXCH heme-binding motif show a distinct asymmetric distribution of orientation. They tend to point between either the heme propionates or between the NA and NB heme nitrogens. Molecular mechanics calculations show that this asymmetry is due to the bonded constraints of the covalent attachment between the heme and the protein. In contrast, the orientations of b-type hemes histidine ligands are found evenly distributed with no preference. Observed histidine heme ligand orientations show no dominating influence of electrostatic interactions between the heme propionates and the ligands. Furthermore, ligands in bis-His hemes are found more frequently perpendicular rather than parallel to each other. These correlations support energetic constraints on ligands that can be used in designing proteins.
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影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
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影响因子：
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通讯作者：
SALEMME, FR
影响因子：
3
作者：
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通讯作者：
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