pH-Dependent Coordination of Pb2+ to Metallothionein2: Structures and Insight into Lead Detoxification | |
He, Yonghui ; Liu, Mengmeng ; Darabedian, Narek ; Liang, Yizeng ; Wu, Deyin ; Xiang, Juan ; Zhou, Feimeng ; Wu DY(吴德印) | |
刊名 | http://dx.doi.org/10.1021/ic402452s |
2014-03-17 | |
关键词 | UNIVERSAL FORCE-FIELD 5-AMINOLEVULINIC ACID DEHYDRATASE MOLECULAR-DYNAMICS SIMULATIONS DENSITY-FUNCTIONAL THEORY AUREUS PI258 CADC CORRELATION-ENERGY PORPHOBILINOGEN SYNTHASE PK(A) VALUES BINDING COMPLEXES |
英文摘要 | National Natural Science Foundation of China [21273288, 20773165]; National Key Basic Research Program of China [2014CB744502]; National Science Foundation [NSF 1112105]; National Institutes of Health [SC1NS070155-01]; Specialized Research Fund for the Doctor Program of Higher Education [20120162110018]; Lead is a toxic heavy metal whose detoxification in organisms is mainly carried out by its coordination with some metalloproteins such as metallothioneins (MTs). Two Pb-MT complexes, named as Pb-7-MT2(I) and Pb-7-MT2(II), form under neutral and weakly acidic conditions, respectively. However, the structures of the two complexes, which are crucial for a better understanding of the detoxification mechanism of Pb-MTs, have not been clearly elucidated. In this Work, coordination of Pb2+ with rabbit liver apo-MT2, as well as with the two individual domains (apo-alpha MT2 and apo-beta MT2) at different pH, were studied by combined spectroscopic (UV-visible, circular dichroism, and NMR) and computational methods. The results showed that in Pb-7-MT2(I) the Pb2+ coordination is in the trigonal pyramidal Pb-S-3 mode, whereas the Pb-7-MT2(II) complex contains mixed trigonal pyramidal Pb-S-3, distorted trigonal pyramidal Pb-S2O1, and distorted quadrilateral pyramidal Pb-S3O1 modes. The O-donor ligand in Pb-7-MT2(II) was identified as the carboxyl groups of the aspartic acid residues at positions 2 and 56. Our studies also revealed that Pb-7-MT2(II) has a greater acid tolerance and coordination stability than Pb-7-MT2(I), thereby retaining the Pb2+ coordination at acidic pH. The higher flexibility of Pb-7-MT2(10 renders it more accessible to lysosomal proteolysis than Pb-7-MT2(I). Similar spectral features were observed in the coordination of Pb2+ by human apo-MT2, suggesting a commonality among mammalian MT2s in the Pb2+ coordination chemistry. |
语种 | 英语 |
出版者 | AMER CHEMICAL SOC |
内容类型 | 期刊论文 |
源URL | [http://dspace.xmu.edu.cn/handle/2288/89349] |
专题 | 化学化工-已发表论文 |
推荐引用方式 GB/T 7714 | He, Yonghui,Liu, Mengmeng,Darabedian, Narek,et al. pH-Dependent Coordination of Pb2+ to Metallothionein2: Structures and Insight into Lead Detoxification[J]. http://dx.doi.org/10.1021/ic402452s,2014. |
APA | He, Yonghui.,Liu, Mengmeng.,Darabedian, Narek.,Liang, Yizeng.,Wu, Deyin.,...&吴德印.(2014).pH-Dependent Coordination of Pb2+ to Metallothionein2: Structures and Insight into Lead Detoxification.http://dx.doi.org/10.1021/ic402452s. |
MLA | He, Yonghui,et al."pH-Dependent Coordination of Pb2+ to Metallothionein2: Structures and Insight into Lead Detoxification".http://dx.doi.org/10.1021/ic402452s (2014). |
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