Weak-field anions displace the histidine ligand in a synthetic heme peptide but not in N-acetylmicroperoxidase-8:: Possible role of heme geometry differences
Weak-field anions displace the histidine ligand in a synthetic heme peptide but not in N-acetylmicroperoxidase-8:: Possible role of heme geometry differences
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DOI：
10.1021/ic060682c
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发表时间：
2007-01-08
影响因子：
4.6
通讯作者：
Benson, David R.
中科院分区：
文献类型：
--
作者：
Cowley, Aaron B.;Benson, David R.
我们最近报道了铁细胞色素c血红素肽N-乙酰微过氧化物酶-8（Fe-III-1）的水和硫醚复合物比合成的、水溶性的、单组氨酸连接的血红素肽（Fe-III-2; Cowley，A. B.; Lukat-Rodgers，G. S.的;罗杰斯，K。的R.;本森，D。R. Biochemistry 2004，43，1656-1666）。在这里，我们报告的研究结果表明，弱场配体承载一个完整的（氟化物，氯化物，氢氧化物）或部分（酚盐，硫氰酸盐）负电荷的配位原子触发解离的轴向His配体在Fe-III-2，但不是在Fe-III-1。我们将Fe-III-1中His连接对弱场阴离子配体比对弱场中性配体更大的敏感性归因于以下现象：（1）阴离子配体比中性配体将Fe-III从卟啉的平均平面拉得更远，这将具有拉紧Fe-III-2中的His-Fe键的效果，和（2）Fe-III-2中的血红素在阴离子结合后可能经历适度的拱起变形，这将使卟啉的His-连接侧凹陷，从而增加卟啉/配体空间相互作用。我们建议，铁-III-1中的血红素的褶皱是一个重要的因素，有助于其抵抗弱场阴离子解离的能力。首先，褶皱应允许His比Fe-III-2中可能的更接近卟啉，从而减少阴离子结合后的键张力。第二，铁III-1的褶皱变形，这是由双共价血红素-肽连接，几乎肯定会防止显着的卟啉圆顶。
We have recently reported that aquo and thioether complexes of the ferric cytochrome c heme peptide N-acetylmicroperoxidase-8 (Fe-III-1) exhibit greater low-spin character than do the corresponding complexes of a synthetic, water-soluble, monohistidine-ligated heme peptide (Fe-III-2; Cowley, A. B.; Lukat-Rodgers, G. S.; Rodgers, K. R.; Benson, D. R. Biochemistry 2004, 43, 1656-1666). Herein we report results of studies showing that weak-field ligands bearing a full (fluoride, chloride, hydroxide) or partial (phenoxide, thiocyanate) negative charge on the coordinating atom trigger dissociation of the axial His ligand in Fe-III-2 but not in Fe-III-1. We attribute the greater sensitivity of His ligation in Fe-III-1 to weak-field anionic ligands than to weak-field neutral ligands to the following phenomena: (1) anionic ligands pull Fe-III further from the mean plane of a porphyrin than do neutral ligands, which will have the effect of straining the His-Fe bond in Fe-III-2, and (2) heme in Fe-III-2 is likely to undergo a modest doming distortion following anion binding that will render the His-ligated side of the porphyrin concave, thereby increasing porphyrin/ligand steric interactions. We propose that ruffling of the heme in Fe-III-1 is an important factor contributing to its ability to resist His dissociation by weak-field anions. First, ruffling should allow His to more closely approach the porphyrin than is possible in Fe-III-2, thereby reducing bond strain following anion binding. Second, the ruffling deformation in Fe-III-1, which is enforced by the double covalent heme-peptide linkage, will almost certainly prevent significant porphyrin doming.