Resonance Raman Spectroscopic Examination of Ferrochelatase-induced Porphyrin Distortion.
Resonance Raman Spectroscopic Examination of Ferrochelatase-induced Porphyrin Distortion.
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DOI：
10.1142/s1088424611003380
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发表时间：
2011-05
影响因子：
1.5
通讯作者：
Ferreira GC
中科院分区：
文献类型：
--
作者：
Franco R;Al-Karadaghi S;Ferreira GC
亚铁螯合酶是血红素生物合成途径的末端酶，催化亚铁插入原卟啉IX中生成血红素。共振拉曼光谱已被用于确定卟啉底物的畸变（模式和程度），这是铁螯合酶催化机制中的关键步骤。鞍形是卟啉与亚铁螯合酶结合后引起的主要平面外变形。我们的分析表明，γ15线的强度，这是分配给一个平面外的卟啉振动，在共振拉曼光谱获得的野生型和变体亚铁螯合酶结合卟啉，与鞍形变形所经历的卟啉底物。进一步分析的三维X-射线结构的细菌，人类和酵母亚铁螯合酶和扭曲的蛋白质结合的卟啉底物和抑制剂的类型和程度，使用正常的结构分解，支持的观点，亚铁螯合酶催化涉及绑定的扭曲的卟啉底物和释放的平坦，金属化的卟啉。
Ferrochelatase, the terminal enzyme of the heme biosynthetic pathway, catalyzes the insertion of ferrous iron into protoporphyrin IX to give heme. Resonance Raman spectroscopy has been instrumental in defining the distortion (mode and extent) of the porphyrin substrate, which is a critical step in the catalytic mechanism of ferrochelatase. Saddling is the predominant porphyrin out-of-plane deformation induced upon binding to ferrochelatase. Our analysis demonstrated that the intensity of the γ15 line, which is assigned to an out-of-plane porphyrin vibration, in resonance Raman spectra obtained for wild-type- and variant ferrochelatase-bound porphyrin, correlates with the saddling deformation undergone by the porphyrin substrate. Further analysis of the three dimensional X-ray structures of bacterial, human and yeast ferrochelatases and the type and extent of distortion of the protein-bound porphyrin substrate and inhibitors using normal structure decomposition, support the view that ferrochelatase catalysis involves binding of a distorted porphyrin substrate and releasing of a flatter, metalated porphyrin.