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dc.contributor.authorHe, Yonghuizh_CN
dc.contributor.authorLiu, Mengmengzh_CN
dc.contributor.authorDarabedian, Narekzh_CN
dc.contributor.authorLiang, Yizengzh_CN
dc.contributor.authorWu, Deyinzh_CN
dc.contributor.authorXiang, Juanzh_CN
dc.contributor.authorZhou, Feimengzh_CN
dc.contributor.author吴德印zh_CN
dc.date.accessioned2015-07-22T03:21:19Z
dc.date.available2015-07-22T03:21:19Z
dc.date.issued2014-03-17zh_CN
dc.identifier.citationINORGANIC CHEMISTRY, 2014,53(6):2822-2830zh_CN
dc.identifier.otherWOS:000333142800012zh_CN
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/89349
dc.descriptionNational 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]zh_CN
dc.description.abstractLead 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.zh_CN
dc.language.isoen_USzh_CN
dc.publisherAMER CHEMICAL SOCzh_CN
dc.source.urihttp://dx.doi.org/10.1021/ic402452szh_CN
dc.subjectUNIVERSAL FORCE-FIELDzh_CN
dc.subject5-AMINOLEVULINIC ACID DEHYDRATASEzh_CN
dc.subjectMOLECULAR-DYNAMICS SIMULATIONSzh_CN
dc.subjectDENSITY-FUNCTIONAL THEORYzh_CN
dc.subjectAUREUS PI258 CADCzh_CN
dc.subjectCORRELATION-ENERGYzh_CN
dc.subjectPORPHOBILINOGEN SYNTHASEzh_CN
dc.subjectPK(A) VALUESzh_CN
dc.subjectBINDINGzh_CN
dc.subjectCOMPLEXESzh_CN
dc.titlepH-Dependent Coordination of Pb2+ to Metallothionein2: Structures and Insight into Lead Detoxificationzh_CN
dc.typeArticlezh_CN


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