A proton transfer network that generates deprotonated tyrosine is a key to producing reactive oxygen species in phototoxic KillerRed protein
文献信息
Wook Lee, Inkoo Kim, Young Min Rhee
KillerRed is the first genetically encoded photosensitizer that can induce cytotoxicity upon light exposure. Nevertheless, its phototoxicity is still lower than that of chemical photosensitizers, and the efforts to further develop KillerRed variants with enhanced phototoxicity have been impeded because the mechanism by which it generates cytotoxic reactive oxygen species (ROS) has remained elusive. To shed light on this issue, we employ quantum mechanics/molecular mechanics (QM/MM) modeling with statistical free energy analysis to examine the photo-induced electron transfer reaction occurring in KillerRed. We identify a deprotonated tyrosine residue (Tyr110) as an electron donor and further show that adjacent glutamate and serine residues play essential roles in deprotonating Tyr110. We also show that water mediation is important in the proton transfer and that protein fluctuations importantly govern the fate of the excited system. We provide clues about why KillerRed can only exhibit a low ROS yield and suggest future directions of mutagenesis toward an enhanced phototoxicity.
期刊推荐

Russian Journal of Bioorganic Chemistry

Russian Chemical Bulletin

Russian Journal of Organic Chemistry

Acta Materialia

Current Opinion in Colloid & Interface Science

Saudi Pharmaceutical Journal

New Journal of Chemistry

Journal of Saudi Chemical Society

Russian Journal of Coordination Chemistry

Nature Medicine
相关文献
Quantum-classical dynamics of the capture of neon atoms by superfluid helium nanodroplets
Miquel Blancafort-Jorquera, Arnau Vilà, Miguel González
DOI: 10.1039/C8CP05140B
Rate constants for collision-induced emission of O2(a1Δg) with He, Ne, Ar, Kr, N2, CO2 and SF6 as collisional partners
DOI: 10.1039/C8CP06231E
Protonation-induced molecular permeation at the oil/water interface in an electric field
DOI: 10.1039/C8CP04028A
Quantum anomalous Hall effect in metal-bis(dithiolene), magnetic properties, doping and interfacing graphene
F. Crasto de Lima, Gerson J. Ferreira, R. H. Miwa
DOI: 10.1039/C8CP03792B
Deformation behavior of an amorphous zeolitic imidazolate framework – from a supersoft material to a complex organometallic alloy
Puja Adhikari, Neng Li, Paul Rulis, Wai-Yim Ching
DOI: 10.1039/C8CP05610B
A comparative study of the structure, stability and energetic performance of 5,5′-bitetrazole-1,1′-diolate based energetic ionic salts: future high energy density materials
B. Moses Abraham, Vikas D. Ghule
DOI: 10.1039/C8CP06635C
Adsorption, surface relaxation and electrolyte structure at Pt(111) electrodes in non-aqueous and aqueous acetonitrile electrolytes
Gary S. Harlow, Iain M. Aldous, Yvonne Gründer, Laurence J. Hardwick, Christopher A. Lucas
DOI: 10.1039/C9CP00499H
Silicene-supported TiO2 nanostructures: a theoretical study of electronic and optical properties
Yesukhei Jagvaral, Qing Guo, Haiying He, Ravindra Pandey
DOI: 10.1039/C9CP00894B
Role of the vibrational contribution in Coulomb explosion of dicationic neon gas clusters: a parallel tempering based study
Sankar Ghorai, Pulak Naskar, Pinaki Chaudhury
DOI: 10.1039/C8CP03779E
您可能还喜欢
如何储存1,2-环己二酮环乙缩醛(CAS号:4746-96-7)?
1,2-环己二酮环乙缩醛应储存在阴凉、干燥、通风良好的地方,避免阳光直射。建议使用密封容器保存,并保持环境温度在室温范围内,远离火源和热源。
Ecopladib(CAS号:381683-92-7)的市场或研究趋势如何?
Ecopladib作为一种新型的药物,主要应用于治疗高胆固醇等疾病。目前,市场和研究趋势显示,Ecopladib因其独特的药理作用而受到关注。随着对心血管疾病治...
2,3-Dimethyl-3H-imidazo[4,5-c]pyridine(CAS号:52538-09-7)通常如何合成?
2,3-二甲基-3H-咪唑[4,5-c]吡啶通常通过咪唑和2,3-二甲基吡啶的缩合反应合成。具体来说,将咪唑和2,3-二甲基吡啶在适当的溶剂中进行加热或加压反应...
2,3,4,5-tetrahydro-1H-3-苯并氮杂环;盐酸盐(CAS号:17379-01-0)的市场或研究趋势如何?
该化合物在药物化学和有机合成中有一定的应用。近年来,随着对新型药物化合物的需求增加,该化合物的研究趋势主要集中在探索其生物活性,尤其是其在神经系统疾病治疗中的潜...
如何储存盐酸甘氨酸丁酯(CAS号:13048-99-2)?
盐酸甘氨酸丁酯应储存在阴凉、干燥、通风良好的地方,避免阳光直射和高温环境,温度应控制在25℃以下。储存容器应密封,避免与空气中的水分和酸性物质接触,以防发生水解...
什么是2-Iodo-N,N-dimethylbenzamide(CAS号:54616-46-5)?
2-碘-N,N-二甲基苯胺是一种有机化合物,化学名为2-Iodo-N,N-dimethylbenzamide。其分子式为C<sub>9</sub>H<sub>1...
5-溴-2-(4H-1,2,4-三唑-4-基)吡啶(CAS号:959240-99-4)的市场或研究趋势如何?
随着医药、农药和新材料领域的发展,该化合物作为关键中间体的应用日益增多。特别是在药物合成中,由于其独特的化学性质,可以用于合成多种药物分子。未来的研究趋势可能集...
2,4-二溴-6-三氟甲基嘧啶(CAS号:785778-00-9)通常如何合成?
2,4-二溴-6-三氟甲基嘧啶通常通过溴化反应合成。首先,将6-三氟甲基嘧啶与溴化剂(如液溴)在适当的溶剂(如二氯甲烷、四氢呋喃)中反应,加入适当的催化剂(如四...
来源期刊
Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.




