Department of Chemistry, University of Oxford, Inorganic Chemistry Laboratory, Oxford OX1 3QR, United Kingdom.
Proteins. 2010 Aug 1;78(10):2349-68. doi: 10.1002/prot.22747.
The characteristics of heme prosthetic groups and their binding sites have been analyzed in detail in a data set of nonhomologous heme proteins. Variations in the shape, volume, and chemical composition of the binding site, in the mode of heme binding and in the number and nature of heme-protein interactions are found to result in significantly different heme environments in proteins with different functions in biology. Differences are also seen in the properties of the apo states of the proteins. The apo states of proteins that bind heme permanently in their functional form show some disorder, ranging from local unfolding in the heme binding pocket to complete unfolding to give a random coil. In contrast, proteins that bind heme transiently are fully folded in their apo and holo states, presumably allowing both apo and holo forms to remain biologically active resisting aggregation or proteolysis. The principles identified here provide a framework for the design of de novo proteins that will exhibit tight heme ligand binding and for the identification of the function of structural genomic target proteins with heme ligands.
已在非同源血红素蛋白数据集内详细分析了血红素辅基及其结合位点的特征。在结合位点的形状、体积和化学组成、血红素结合方式以及血红素-蛋白相互作用的数量和性质方面的变化导致生物学中具有不同功能的蛋白质中血红素环境显著不同。在蛋白质的apo 状态的性质上也存在差异。以其功能形式永久结合血红素的蛋白质的 apo 状态显示出一定程度的无序，范围从血红素结合口袋中的局部展开到完全展开以形成无规卷曲。相比之下，以其 apo 和 holo 状态结合血红素的蛋白质是完全折叠的，这可能允许 apo 和 holo 形式保持生物活性，抵抗聚集或蛋白水解。此处确定的原则为设计将表现出紧密血红素配体结合的新型蛋白质以及鉴定具有血红素配体的结构基因组靶蛋白的功能提供了一个框架。
