Navigating within thiamine diphosphate‐dependent decarboxylases: Sequences, structures, functional positions, and binding sites
Navigating within thiamine diphosphate‐dependent decarboxylases: Sequences, structures, functional positions, and binding sites
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DOI：
10.1002/prot.25706
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发表时间：
2019-09
期刊：
影响因子：
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通讯作者：
Patrick C. F. Buchholz;V. Ferrario;M. Pohl;L. Gardossi;J. Pleiss
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文献类型：
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作者：
Patrick C. F. Buchholz;V. Ferrario;M. Pohl;L. Gardossi;J. Pleiss
硫胺素二磷酸依赖性脱羧酶在各种反应中催化C → C键的裂解和形成，这些反应已被分配到不同的同源序列家族。这项工作比较了53个ThDP依赖性脱羧酶与已知的晶体结构。序列和结构信息进行了协同分析，并通过统计方法（主成分分析和主坐标分析），使复杂性降低的数据进行了分析的全局和局部性能。局部和全局获得的不同结果，即与整体蛋白质序列或结构相比的单个位置，揭示了分配分离的同源家族的挑战。本文应用的方法支持酶家族的比较和功能相关位置的鉴定。ThDP依赖性脱羧酶家族的研究结果强调，单独的全局序列同一性不足以区分酶的功能。相反，局部序列相似性，通过比较结构上等同的位置，允许更好地导航内的几组同源酶。通过考虑结构信息，如活性位点性质的BioGPS分析或成对结构重叠，进一步增强同源序列之间的区分。预期本文应用的方法可转移到其他酶家族，以促进同源蛋白质序列的家族分配。
Thiamine diphosphate‐dependent decarboxylases catalyze both cleavage and formation of CC bonds in various reactions, which have been assigned to different homologous sequence families. This work compares 53 ThDP‐dependent decarboxylases with known crystal structures. Both sequence and structural information were analyzed synergistically and data were analyzed for global and local properties by means of statistical approaches (principle component analysis and principal coordinate analysis) enabling complexity reduction. The different results obtained both locally and globally, that is, individual positions compared with the overall protein sequence or structure, revealed challenges in the assignment of separated homologous families. The methods applied herein support the comparison of enzyme families and the identification of functionally relevant positions. The findings for the family of ThDP‐dependent decarboxylases underline that global sequence identity alone is not sufficient to distinguish enzyme function. Instead, local sequence similarity, defined by comparisons of structurally equivalent positions, allows for a better navigation within several groups of homologous enzymes. The differentiation between homologous sequences is further enhanced by taking structural information into account, such as BioGPS analysis of the active site properties or pairwise structural superimpositions. The methods applied herein are expected to be transferrable to other enzyme families, to facilitate family assignments for homologous protein sequences.