Role of the Chemical Environment beyond the Coordination Site: Structural Insight into FeIII Protoporphyrin Binding to Cysteine-Based Heme-Regulatory Protein Motifs
Role of the Chemical Environment beyond the Coordination Site: Structural Insight into FeIII Protoporphyrin Binding to Cysteine-Based Heme-Regulatory Protein Motifs
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DOI：
10.1002/cbic.201500331
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发表时间：
2015-10-12
期刊：
影响因子：
3.2
通讯作者：
Imhof, Diana
中科院分区：
文献类型：
--
作者：
Brewitz, Hans Henning;Kuehl, Toni;Imhof, Diana
血红素作为一种瞬时调节分子的重要性已成为生物化学研究的主要焦点。然而，关于瞬时血红素-蛋白质相互作用的分子基础的详细信息仍然缺乏。我们报道了用UV/Vis、共振拉曼和2D-核磁共振光谱方法相结合的方法对Fe-III血红素多肽络合物的结构进行了深入的分析。这些实验揭示了对中心铁离子的配位以及与原卟啉IX相互作用的氨基酸序列的空间排列。基于半胱氨酸的多肽表现出不同的血红素结合行为，这是因为在未结合血红素的状态下，存在有序、部分有序和无序的构象。因此，血红素结合模式显然是铁离子与半胱氨酸配位的铁离子周围残基的性质和灵活性的结果。我们的分析揭示了血红素与蛋白质中的血红素调节基序瞬时结合的场景，并表明需要进行彻底的结构分析才能揭示血红素如何改变特定蛋白质的结构和功能。
The importance of heme as a transient regulatory molecule has become a major focus in biochemical research. However, detailed information about the molecular basis of transient heme-protein interactions is still missing. We report an in-depth structural analysis of Fe-III heme-peptide complexes by a combination of UV/Vis, resonance Raman, and 2D-NMR spectroscopic methods. The experiments reveal insights both into the coordination to the central iron ion and into the spatial arrangement of the amino acid sequences interacting with protoporphyrin IX. Cysteine-based peptides display different heme-binding behavior as a result of the existence of ordered, partially ordered, and disordered conformations in the heme-unbound state. Thus, the heme-binding mode is clearly the consequence of the nature and flexibility of the residues surrounding the iron ion coordinating cysteine. Our analysis reveals scenarios for transient binding of heme to heme-regulatory motifs in proteins and demonstrates that a thorough structural analysis is required to unravel how heme alters the structure and function of a particular protein.