Different Behaviors of a Substrate in P450 Decarboxylase and Hydroxylase Reveal Reactivity-Enabling Actors.
Different Behaviors of a Substrate in P450 Decarboxylase and Hydroxylase Reveal Reactivity-Enabling Actors.
复制标题
DOI：
10.1038/s41598-018-31237-4
复制
发表时间：
2018-08-27
影响因子：
4.6
通讯作者：
Crowley MF
中科院分区：
文献类型：
--
作者：
Bharadwaj VS;Kim S;Guarnieri MT;Crowley MF
利用可再生原料生产燃料的生物途径为我们迈向可持续未来的努力带来了重大希望。脂肪酸脱羧酶 (OleTJE) 是一种细胞色素 P450 酶，可将长链和中链脂肪酸转化为末端烯烃，在结构、底物范围和机制方面与羟化酶细胞色素 P450 (P450BSβ) 具有显着相似性。最近的报告表明，当血红素处于铁羟基（化合物 II）状态时，这些酶的催化途径会分叉。尽管存在显着的相似性，但它们不同特征的野生型反应性的基本基础仍然不明确。在这里，我们开发点电荷、修改参数并报告这一关键中间步骤的分子模拟。据观察，活性位点的水占有率和底物迁移率是两种酶在化合物 II 状态下的重要区别因素，并证实了最近的实验假设。除了羟化酶中底物迁移率的增加（这可能对羟基化的反弹机制产生影响）之外，OleTJE 的特征还在于底物羧酸根基团与活性位点精氨酸的结合力更强，这表明它是脱羧的重要促进因素。
Biological routes to the production of fuels from renewable feedstocks hold significant promise in our efforts towards a sustainable future. The fatty acid decarboxylase enzyme (OleTJE) is a cytochrome P450 enzyme that converts long and medium chain fatty acids to terminal alkenes and shares significant similarities in terms of structure, substrate scope and mechanism with the hydroxylase cytochrome P450 (P450BSβ). Recent reports have demonstrated that catalytic pathways in these enzymes bifurcate when the heme is in its iron-hydroxo (compound II) state. In spite of significant similarities, the fundamental underpinnings of their different characteristic wild-type reactivities remain ambiguous. Here, we develop point charges, modified parameters and report molecular simulations of this crucial intermediate step. Water occupancies and substrate mobility at the active site are observed to be vital differentiating aspects between the two enzymes in the compound II state and corroborate recent experimental hypotheses. Apart from increased substrate mobility in the hydroxylase, which could have implications for enabling the rebound mechanism for hydroxylation, OleTJE is characterized by much stronger binding of the substrate carboxylate group to the active site arginine, implicating it as an important enabling actor for decarboxylation.
登录
查看更多内容
影响因子：
6.3
作者：
Liu Y;Wang C;Yan J;Zhang W;Guan W;Lu X;Li S
通讯作者：
Li S
影响因子：
64.8
作者：
Choi, Yong Jun;Lee, Sang Yup
通讯作者：
Lee, Sang Yup
影响因子：
15
作者：
Grant, Job L.;Hsieh, Chun H.;Makris, Thomas M.
通讯作者：
Makris, Thomas M.
P450 OleT(JE)的分子基础：底物结合机制和主要途径的研究
影响因子：
3.5
作者：
Du, Juan;Liu, Lin;Yang, Jian Ming
通讯作者：
Yang, Jian Ming
P450 脂肪酸脱羧酶 OleTJE 的诱变和氧化还原伙伴分析
影响因子：
4.6
作者：
Fang B;Xu H;Liu Y;Qi F;Zhang W;Chen H;Wang C;Wang Y;Yang W;Li S
通讯作者：
Li S