The modular structure of ThDP‐dependent enzymes
The modular structure of ThDP‐dependent enzymes
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DOI：
10.1002/prot.24615
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发表时间：
2014-10
期刊：
影响因子：
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通讯作者：
Constantin Vogel;J. Pleiss
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文献类型：
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作者：
Constantin Vogel;J. Pleiss
二磷酸硫胺素 (ThDP) 依赖性酶形成多样化的蛋白质家族，分为九个超家族。辅因子 ThDP 结合在两个催化结构域（PYR 和 PP 结构域）之间的界面处。九个超家族被分配给五种不同的结构体系。两个超家族，磺基丙酮酸脱羧酶和 α-酮酸脱氢酶 2，由单独的 PYR 和 PP 结构域组成。氧化还原酶超家族属于单体内/PYR-PP 类型，具有 N 末端 PYR 和随后的 PP 结构域。活性酶与结合在同一单体的 PYR 和 PP 结构域之间界面的 ThDP 辅因子形成同二聚体。脱羧酶属于单体间/PYR-PP 类型，辅因子结合在不同单体的结构域之间。 1-脱氧-d-木酮糖-5-磷酸合酶属于单体内/PP-PYR 类型。转酮醇酶、α-酮戊二酸脱氢酶和 α-酮酸脱氢酶 1 属于单体间/PP-PYR 类型。对于磷酸丙酮酸脱羧酶，由于缺乏结构信息，不可能对结构体系进行明确评估。通过应用基于结构的域比对方法，识别并比对了超过 62,000 个 PYR 和 PP 域的序列。尽管不同超家族之间催化结构域的序列相似性较低，但有七个位置被鉴定为高度保守，包括辅因子结合GDGX24,27N基序、辅因子激活谷氨酸以及PYR和PP结构域中两个结构等效的甘氨酸。提出了 ThDP 依赖性酶的进化途径，通过三个基本进化事件解释了该家族的序列和结构多样性：结构域招募、结构域连接和催化结构域的结构重排。蛋白质 2014; 82：2523–2537。 © 2014 Wiley 期刊公司。
Thiamine diphosphate (ThDP)‐dependent enzymes form a diverse protein family which was classified into nine superfamilies. The cofactor ThDP is bound at the interface between two catalytic domains, the PYR and the PP domain. The nine superfamilies were assigned to five different structural architectures. Two superfamilies, the sulfopyruvate decarboxylases and α‐ketoacid dehydrogenases 2, consist of separate PYR and PP domains. The oxidoreductase superfamily is of the intra‐monomer/PYR‐PP type with an N‐terminal PYR and a subsequent PP domain. The active enzymes form homodimers with the ThDP cofactor bound at the interface between a PYR and a PP domain of the same monomer. Decarboxylases are of the inter‐monomer/PYR‐PP type with the cofactor bound between domains from different monomers. 1‐Deoxy‐d‐xylulose‐5‐phosphate synthases are of the intra‐monomer/PP‐PYR type. The transketolases, α‐ketoglutarate dehydrogenases, and α‐ketoacid dehydrogenases 1 are of the inter‐monomer/PP‐PYR type. For the phosphonopyruvate decarboxylases, definitive assessment of the structural architecture is not possible due to lack of structure information. By applying a structure‐based domain alignment method, sequences of more than 62,000 PYR and PP domains were identified and aligned. Although the sequence similarity of the catalytic domains is low between different superfamilies, seven positions were identified to be highly conserved, including the cofactor binding GDGX24,27N motif, the cofactor‐activating glutamic acid, and two structurally equivalent glycines in both the PYR and the PP domain. An evolutionary pathway of ThDP‐dependent enzymes is proposed which explains the sequence and structure diversity of this family by three basic evolutionary events: domain recruitment, domain linkage, and structural rearrangement of catalytic domains. Proteins 2014; 82:2523–2537. © 2014 Wiley Periodicals, Inc.