色氨酸合酶
变构调节
蛋白质亚单位
酶
四级结构
索引
生物
吲哚试验
生物化学
色氨酸
活动站点
化学
生物物理学
遗传学
氨基酸
基因
单核苷酸多态性
基因型
作者
Jennifer R. Fleming,Michael Schupfner,Florian Büsch,Arnaud Baslé,Alexander Ehrmann,Reinhard Sterner,Olga Mayans
标识
DOI:10.1016/j.jmb.2018.10.013
摘要
Tryptophan synthase (TrpS) is a heterotetrameric αββα enzyme that exhibits complex substrate channeling and allosteric mechanisms and is a model system in enzymology. In this work, we characterize proposed early and late evolutionary states of TrpS and show that they have distinct quaternary structures caused by insertions-deletions of sequence segments (indels) in the β-subunit. Remarkably, indole hydrophobic channels that connect α and β active sites have re-emerged in both TrpS types, yet they follow different paths through the β-subunit fold. Also, both TrpS geometries activate the α-subunit through the rearrangement of loops flanking the active site. Our results link evolutionary sequence changes in the enzyme subunits with channeling and allostery in the TrpS enzymes. The findings demonstrate that indels allow protein quaternary architectures to escape "minima" in the evolutionary landscape, thereby overcoming the conservational constraints imposed by existing functional interfaces and being free to morph into new mechanistic enzymes.
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