Cobamide Structure Depends on Both Lower Ligand Availability and CobT Substrate Specificity
Cobamide Structure Depends on Both Lower Ligand Availability and CobT Substrate Specificity
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DOI：
10.1016/j.chembiol.2013.08.006
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发表时间：
2013-10-24
影响因子：
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通讯作者：
Taga, Michiko E.
中科院分区：
文献类型：
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作者：
Crofts, Terence S.;Seth, Erica C.;Taga, Michiko E.
维生素B-12是维生素B-12辅助因子家族的成员，在多种代谢过程中起作用，仅由原核生物合成。不同生物产生的钴胺在下轴配体的结构上是不同的。在这里，我们探索的分子因素，控制特异性的结合下配体碱基进入蜘蛛。我们发现，cobT基因产物激活下配体碱基的附着，限制了细菌可以结合的下配体碱基的范围。此外，我们证明了CobT的底物特异性可以通过改变两个活性位点残基来预测地改变。这些结果表明，cobT同源物的序列变化有助于cobide结构的多样性。这种分析可以为设计特定的共聚物生产和理解共聚物依赖过程开辟新的途径。
Cobamides are members of the vitamin B-12 family of cofactors that function in a variety of metabolic processes and are synthesized only by prokaryotes. Cobamides produced by different organisms vary in the structure of the lower axial ligand. Here we explore the molecular factors that control specificity in the incorporation of lower ligand bases into cobamides. We find that the cobT gene product, which activates lower ligand bases for attachment, limits the range of lower ligand bases that can be incorporated by bacteria. Furthermore, we demonstrate that the substrate specificity of CobT can be predictably altered by changing two active site residues. These results demonstrate that sequence variations in cobT homologs contribute to cobamide structural diversity. This analysis could open new routes to engineering specific cobamide production and understanding cobamide-dependent processes.