Cofactor Dynamics Couples the Protein Surface to the Heme in Cytochrome c, Facilitating Electron Transfer.
Cofactor Dynamics Couples the Protein Surface to the Heme in Cytochrome c, Facilitating Electron Transfer.
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辅因子动力学将蛋白质表面与细胞色素 c 中的血红素偶联，促进电子转移。
DOI：
10.1021/acs.jpcb.2c01632
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Warren,JeffreyJ
中科院分区：
文献类型：
--
作者：
Shen,William;Teo,RuijieD;Beratan,DavidN;Warren,JeffreyJ
电子在生物大分子中的传递和在生物传递网络中的传递对于生物能量学和生物催化具有重要意义。更一般地说，了解将埋藏的金属辅因子连接到其他辅因子和蛋白质表面的途径如何影响金属蛋白的生物化学是至关重要的。在电子转移（ET）方面，最强的耦合途径通常包括共价和氢键网络，具有有限数量的贯通空间接触。在本文中，我们着手确定通过细胞色素（cyt）c中已建立的血红素-表面隧穿途径参与ET的氢键的相对作用（即，血红素-W59-D60-E61-N62）。通过共价修饰N62C残基，将钌三（二亚胺）光氧化剂置于62位，产生了一系列cytcvariants。令人惊讶的是，其中H-键合残基W59和D60被替换的变体（即，W59F和D60A）显示从亚铁血红素到Ru（III）的ET率没有变化。相反，改变替代隧穿途径的组成（即，血红素-M64-N63-C62）与M64L取代显示血红素-Ru ET的速率降低2倍。该途径涉及血红素和M64残基之间的空间穿隧步骤，并且这样的步骤通常是不利的。为了合理化为什么血红素-M64-N63-C62是优选的，采用分子动力学（MD）模拟和途径分析。这些模拟结果表明，血红素钌ET率的变化是由于不同的构象与压缩的供体-受体距离，由102 μ m的路径距离，在M64-含有蛋白质相比，M64L蛋白。距离的变化与电子耦合的变化相关，电子耦合的变化与实验观察到的血红素-Ru ET速率符合雅阁。值得注意的是，蛋白质核心的M64L变异转化为蛋白质表面辅因子动力学的变化。分子动力学模拟确定的表面变化包括动态阴离子− π和偶极-偶极相互作用。这些相互作用通过促进关键耦合途径中的贯穿空间隧穿距离的减小来影响隧穿途径和ET速率的强度。
Electron transport through biomolecules and in biological transport networks is of great importance to bioenergetics and biocatalysis. More generally, it is of crucial importance to understand how the pathways that connect buried metallocofactors to other cofactors, and to protein surfaces, affect the biological chemistry of metalloproteins. In terms of electron transfer (ET), the strongest coupling pathways usually comprise covalent and hydrogen bonded networks, with a limited number of through-space contacts. Herein, we set out to determine the relative roles of hydrogen bonds involved in ET via an established heme-to-surface tunneling pathway in cytochrome (cyt)c(i.e., heme-W59-D60-E61-N62). A series of cytcvariants were produced where a ruthenium tris(diimine) photooxidant was placed at position 62 via covalent modification of the N62C residue. Surprisingly, variants where the H-bonding residues W59 and D60 were replaced (i.e., W59F and D60A) showed no change in ET rate from the ferrous heme to Ru(III). In contrast, changing the composition of an alternative tunneling pathway (i.e., heme-M64-N63-C62) with the M64L substitution shows a factor of 2 decrease in the rate of heme-to-Ru ET. This pathway involves a through-space tunneling step between the heme and M64 residue, and such steps are usually disfavored. To rationalize why the heme-M64-N63-C62 is preferred, molecular dynamics (MD) simulations and Pathways analysis were employed. These simulations show that the change in heme–Ru ET rates is attributed to different conformations with compressed donor–acceptor distances, by ∼2 Å in pathway distance, in the M64-containing protein as compared to the M64L protein. The change in distance is correlated with changes in the electronic coupling that are in accord with the experimentally observed heme–Ru ET rates. Remarkably, the M64L variation at the core of the protein translates to changes in cofactor dynamics at the protein surface. The surface changes identified by MD simulations include dynamic anion−π and dipole–dipole interactions. These interactions influence the strength of tunneling pathways and ET rates by facilitating decreases in through-space tunneling distances in key coupling pathways.
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影响因子：
15
作者：
Tezcan, FA;Winkler, JR;Gray, HB
通讯作者：
Gray, HB
锌取代细胞色素c及其Ru(NH3)5(histidine-33)衍生物的电子转移动力学
DOI：
--
发表时间：
1988
期刊：
影响因子：
--
作者：
H. Elias;M. Chou;J. Winkler
通讯作者：
J. Winkler
影响因子：
2.9
作者：
BERRY, EA;TRUMPOWER, BL
通讯作者：
TRUMPOWER, BL
通过半合成进行细胞色素 c 的蛋白质工程：谷氨酸 66 处的取代。
DOI：
--
发表时间：
1986
期刊：
Protein Engineering
影响因子：
--
作者：
C. Wallace;B. Corthésy
通讯作者：
B. Corthésy
影响因子：
18.3
作者：
Beratan, David N.;Skourtis, Spiros S.;Balabin, Ilya A.;Balaeff, Alexander;Keinan, Shahar;Venkatramani, Ravindra;Xiao, Dequan
通讯作者：
Xiao, Dequan