Allomorphy as a mechanism of post-translational control of enzyme activity.
Allomorphy as a mechanism of post-translational control of enzyme activity.
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DOI：
10.1038/s41467-020-19215-9
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发表时间：
2020-11-02
影响因子：
16.6
通讯作者：
Waltho JP
中科院分区：
文献类型：
--
作者：
Wood HP;Cruz-Navarrete FA;Baxter NJ;Trevitt CR;Robertson AJ;Dix SR;Hounslow AM;Cliff MJ;Waltho JP
酶调节对于生命系统的代谢适应性至关重要。酶活性的精细控制通常通过翻译后机制，如变构或变链来实现。乳酸乳球菌β-磷酸葡萄糖变位酶（β-PGM）是一种磷酸转移酶，通过β-葡萄糖1，6-二磷酸将β-葡萄糖1-磷酸异构化为葡萄糖6-磷酸，完成海藻糖和麦芽糖的完全催化。令人惊讶的是，作为糖酵解的守门人，尚未报道βPGM的精细控制机制。在这里，我们描述了同质异晶，酶活性的翻译后控制机制。在βPGM中，K145-P146肽键的异构化导致两种构象异构体的群体，这两种构象异构体由于K145侧链的重新定位而具有不同的活性。体内磷酸化剂，如果糖1，6-二磷酸，产生两种构象异构体的磷酸化形式，导致活性的滞后期，直到更活跃的磷酸化构象异构体占主导地位。相比之下，反应中间体β-葡萄糖1，6-二磷酸（其浓度取决于β-葡萄糖1-磷酸浓度）将构象转换和磷酸化步骤偶联，导致快速生成更有活性的磷酸化构象异构体。在使不同的行为为不同的异形激活剂，异形允许生物体最大限度地提高其对环境变化的反应，同时最大限度地减少有价值的代谢物的转移。β-磷酸葡萄糖变位酶（β-PGM）是乳酸乳球菌（Lactococcus lactis）产生的一种磷酸转移酶，是海藻糖和麦芽糖催化转化所必需的。对多个βPGM结构和酶活性的耦合分析导致提出了异晶性-一种控制酶活性的翻译后机制。
Enzyme regulation is vital for metabolic adaptability in living systems. Fine control of enzyme activity is often delivered through post-translational mechanisms, such as allostery or allokairy. β-phosphoglucomutase (βPGM) from Lactococcus lactis is a phosphoryl transfer enzyme required for complete catabolism of trehalose and maltose, through the isomerisation of β-glucose 1-phosphate to glucose 6-phosphate via β-glucose 1,6-bisphosphate. Surprisingly for a gatekeeper of glycolysis, no fine control mechanism of βPGM has yet been reported. Herein, we describe allomorphy, a post-translational control mechanism of enzyme activity. In βPGM, isomerisation of the K145-P146 peptide bond results in the population of two conformers that have different activities owing to repositioning of the K145 sidechain. In vivo phosphorylating agents, such as fructose 1,6-bisphosphate, generate phosphorylated forms of both conformers, leading to a lag phase in activity until the more active phosphorylated conformer dominates. In contrast, the reaction intermediate β-glucose 1,6-bisphosphate, whose concentration depends on the β-glucose 1-phosphate concentration, couples the conformational switch and the phosphorylation step, resulting in the rapid generation of the more active phosphorylated conformer. In enabling different behaviours for different allomorphic activators, allomorphy allows an organism to maximise its responsiveness to environmental changes while minimising the diversion of valuable metabolites. β-phosphoglucomutase (βPGM) from Lactococcus lactis is a phosphoryl transfer enzyme required for catabolism of trehalose and maltose. Coupled analyses of multiple βPGM structures and enzymatic activity lead to the proposal of allomorphy — a post-translational mechanism controlling enzyme activity.
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影响因子：
2.9
作者：
Dai, Jianying;Finci, Lorenzo;Zhang, Chunchun;Lahiri, Sushmita;Zhang, Guofeng;Peisach, Ezra;Allen, Karen N.;Dunaway-Mariano, Debra
通讯作者：
Dunaway-Mariano, Debra
DOI：
10.1002/anie.201509477
发表时间：
2016-03-01
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Jin Y;Molt RW Jr;Waltho JP;Richards NG;Blackburn GM
通讯作者：
Blackburn GM
影响因子：
4.4
作者：
Goel, Anisha;Santos, Filipe;Molenaar, Douwe
通讯作者：
Molenaar, Douwe
影响因子：
4.8
作者：
Andersson, U;Levander, F;Rådström, P
通讯作者：
Rådström, P
影响因子：
15
作者：
Cliff, Matthew J.;Bowler, Matthew W.;Waltho, Jonathan P.
通讯作者：
Waltho, Jonathan P.