Dynamic, electrostatic model for the generation and control of high-energy radical intermediates by a coenzyme B₁₂-dependent enzyme.
Dynamic, electrostatic model for the generation and control of high-energy radical intermediates by a coenzyme B₁₂-dependent enzyme.
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DOI：
10.1002/cbic.201300420
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发表时间：
2013-09-02
期刊：
影响因子：
3.2
通讯作者：
Scrutton, Nigel S.
中科院分区：
文献类型：
--
作者：
Chen, Zhi-Gang;Zietek, Monika A.;Russell, Henry J.;Tait, Shirley;Hay, Sam;Jones, Alex R.;Scrutton, Nigel S.
High-energy radical species are widespread in biology as transient reaction intermediates and free radicals. The control of these extremely reactive molecules is crucial to limit oxidative stress and promote healthy physiological function.[1] In some cases this reactivity can be harnessed by a system to do useful work.[2] Over two decades ago RØtey discussed how energy can be “borrowed” from an enzyme to effect an unlikely chemical change.[3] In the case of coenzymeB12-dependent enzymes,[4] this energy is “lent” in the form of radical intermediates, which are formed upon substrate binding by CoÀC bond homolysis in the cofactor. The energy is then returned by radical pair recombination after turnover (Scheme 1).The key is the way in which the protein generates the radicals and then prevents these high-energy intermediates from stabilising (ie, dropping to a lower energy) through side reactions. Thus, the borrowed energy is channelled to the desired chemical change. Despite ample data demonstrating the role of radicals in coenzyme B12-dependent enzymes, there is less direct evidence for how the protein controls them.[5] Herein, we present data that suggest that a single point mutation can have a significant impact on CoÀC bond homolysis and the control of the radical trajectory and reactivity in coenzyme B12-dependent ethanolamine ammonia lyase (EAL). The data show that the size and negative charge of an active-site glutamate (E287, Figure 1) contribute variously to 1) apparent substrate
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影响因子：
16.6
作者：
Jones, Alex R.;Hardman, Samantha J. O.;Scrutton, Nigel S.
通讯作者：
Scrutton, Nigel S.
影响因子：
2.9
作者：
Bender, Guenes;Poyner, Russell R.;Reed, George H.
通讯作者：
Reed, George H.
影响因子：
2.1
作者：
Monera, Oscar D.;Sereda, Terrance J.;Hodges, Robert S.
通讯作者：
Hodges, Robert S.
影响因子：
2.9
作者：
Mancia, F;Smith, GA;Evans, PR
通讯作者：
Evans, PR
影响因子：
2.9
作者：
Bandarian, V;Reed, GH
通讯作者：
Reed, GH