期刊
INORGANIC CHEMISTRY
卷 53, 期 6, 页码 2822-2830出版社
AMER CHEMICAL SOC
DOI: 10.1021/ic402452s
关键词
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资金
- 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]
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [1112105] Funding Source: National Science Foundation
- Division Of Human Resource Development
- Direct For Education and Human Resources [0932421] Funding Source: National Science Foundation
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.
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