Crystal Structure of Type III Glutamine Synthetase: Surprising Reversal of the Inter-Ring Interface
Crystal Structure of Type III Glutamine Synthetase: Surprising Reversal of the Inter-Ring Interface
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DOI：
10.1016/j.str.2011.02.001
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发表时间：
2011-04-13
期刊：
影响因子：
5.7
通讯作者：
Sewell, Trevor
中科院分区：
文献类型：
--
作者：
van Rooyen, Jason M.;Abratt, Valerie R.;Sewell, Trevor
谷氨酰胺合成酶是氮代谢所必需的普遍存在的同源寡聚酶。与I型和II型不同，它们在结构和功能上都有很好的描述，尽管它们广泛存在，但较大的III型的特征很差。理解这种分歧的结构基础和类型特异性抑制剂的设计的影响，因此，是不可能的。第一个晶体结构的GSIII酶，在这里，揭示了GS催化折叠的保护，但蛋白质-配体相互作用的细微差异，建议可能的途径设计GSIII抑制剂。尽管有这些相似之处，GSIII酶的分歧可以通过四级结构的差异来解释。出乎意料的是，GSIII十二聚体的两个六聚体环在相对于I型和II型的相对表面上缔合。GS四级结构的多样性表明，在所有GS酶的双环结构的演变nonallosteric的作用。
Glutamine synthetases are ubiquitous, homo-oligomeric enzymes essential for nitrogen metabolism. Unlike types I and II, which are well described both structurally and functionally, the larger, type Ills are poorly characterized despite their widespread occurrence. An understanding of the structural basis for this divergence and the implications for design of type-specific inhibitors has, therefore, been impossible. The first crystal structure of a GSIII enzyme, presented here, reveals a conservation of the GS catalytic fold but subtle differences in protein-ligand interactions suggest possible avenues for the design GSIII inhibitors. Despite these similarities, the divergence of the GSIII enzymes can be explained by differences in quaternary structure. Unexpectedly, the two hexameric rings of the GSIII dodecamer associate on the opposite surface relative to types I and II. The diversity of GS quaternary structures revealed here suggests a nonallosteric role for the evolution of the double-ringed architecture seen in all GS enzymes.