Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487, USA.
Arch Biochem Biophys. 2012 Mar 15;519(2):202-9. doi: 10.1016/j.abb.2011.10.009. Epub 2011 Oct 19.
The manipulation of modular regulatory domains from allosteric enzymes represents a possible mechanism to engineer allostery into non-allosteric systems. Currently, there is insufficient understanding of the structure/function relationships in modular regulatory domains to rationally implement this methodology. The LeuA dimer regulatory domain represents a well-conserved, novel fold responsible for the regulation of two enzymes involved in branched chain amino acid biosynthesis, α-isopropylmalate synthase and citramalate synthase. The LeuA dimer regulatory domain is responsible for the feedback inhibition of these enzymes by their respective downstream products. Both enzymes display multidomain architecture with a conserved N-terminal TIM barrel catalytic domain and a C-terminal (βββα)2 LeuA dimer domain joined by a flexible linker region. Due to the similarity of three-dimensional structure and catalytic mechanism combined with low sequence similarity, we propose these enzymes can be classified as members of the LeuA dimer superfamily. Despite their similarity, members of the LeuA dimer superfamily display diversity in their allosteric mechanisms. In this review, structural aspects of the LeuA dimer superfamily are discussed followed by three examples highlighting the diversity of allosteric mechanisms in the LeuA dimer superfamily.
操纵变构酶的模块化调节域代表了将变构作用工程应用于非变构系统的一种可能机制。目前，对于模块化调节域的结构/功能关系的理解还不足以合理地实施这种方法。LeuA 二聚体调节域代表了一种保守的新型折叠，负责调节两种参与支链氨基酸生物合成的酶，即α-异丙基苹果酸合酶和柠檬酸合酶。LeuA 二聚体调节域负责反馈抑制这些酶的各自下游产物。这两种酶都具有多结构域的结构，包括保守的 N 端 TIM 桶催化结构域和 C 端（βββα）2 LeuA 二聚体结构域，由一个柔性连接区连接。由于三维结构和催化机制的相似性以及低序列相似性，我们提出这些酶可以被归类为 LeuA 二聚体超家族的成员。尽管它们相似，但 LeuA 二聚体超家族的成员在变构机制上表现出多样性。在这篇综述中，我们讨论了 LeuA 二聚体超家族的结构方面，然后通过三个例子强调了 LeuA 二聚体超家族变构机制的多样性。
