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首页> 外文期刊>Biochemistry >A Conserved cis-Proline Precludes Metal Binding by the Active Site Thiolates in Members of the Thioredoxin Family of Proteins
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A Conserved cis-Proline Precludes Metal Binding by the Active Site Thiolates in Members of the Thioredoxin Family of Proteins

机译：一个保守的顺脯氨酸排除了硫氧还蛋白家族蛋白成员中的活性位点硫醇盐的金属结合

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Many thioredoxin-fold proteins possess a conserved cis-proline located in their C-terminal portions.This residue,as well as catalytic and resolving cysteines,is a key functional group in the active sites of these thiol-disulfide oxidoreductases.However,the specific function of the proline is poorly understood,and some thioredoxin-fold proteins lack this residue.Herein,we found that mutation of a cis-proline,Pro75,in human thioredoxin to serine,threonine,or alanine leads to the formation of an Fe2-S2 cluster in this protein.Further mutagenesis studies revealed that the first cysteine in the CxxC motif and a cysteine in the C-terminal region of the protein were responsible for metal binding.Replacement of Pro75 with arginine,a residue that occurs in place of Pro in peroxiredoxins,also led to the formation of the cluster in the thioredoxin.In addition,we found that mutation of the TxxC active site in a peroxiredoxin to the CxxC form could lead to coordination of an Fe2-S2 cluster in these proteins in vitro.Scol,a distantly related thioredoxin-fold protein,has histidine in place of the cis-proline,and this residue binds copper.The Pro75His mutation led to increased copper binding by human thioredoxin when cells were grown in the presence of this trace element.Taken together,our data suggest that an important function of Pro75 in human thioredoxin,and likely other members of this superfamily,is to prevent metal binding by the reactive thiolate-based active site.
机译：许多硫氧还蛋白折叠蛋白在其C端部分具有一个保守的顺脯氨酸。该残基以及催化和可分解的半胱氨酸是这些硫醇-二硫键氧化还原酶活性位点中的关键功能基团。人们对脯氨酸的功能了解甚少，有些硫氧还蛋白折叠蛋白缺少该残基。在这里，我们发现人硫氧还蛋白中的顺式脯氨酸Pro75突变为丝氨酸，苏氨酸或丙氨酸会导致Fe2- S2聚集在该蛋白质中。进一步的诱变研究表明，CxxC基序中的第一个半胱氨酸和该蛋白质C端区域中的一个半胱氨酸负责金属结合。精氨酸取代Pro75，一个残基代替Pro此外，我们发现过氧化物酶的TxxC活性位点突变为CxxC形式可能导致Fe2-S2簇的协调。远距相关的硫氧还蛋白折叠蛋白Scol具有组氨酸代替顺式脯氨酸，并且该残基与铜结合.Pro75His突变导致人硫氧还蛋白在细胞生长时与铜的结合增加综上所述，我们的数据表明，Pro75在人硫氧还蛋白以及该超家族的其他成员中的重要功能是防止基于硫醇盐的活性位点与金属结合。

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