Multitargeting by curcumin as revealed by molecular interaction studies.
Multitargeting by curcumin as revealed by molecular interaction studies.
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DOI：
10.1039/c1np00051a
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发表时间：
2011-11
影响因子：
11.9
通讯作者：
Aggarwal BB
中科院分区：
文献类型：
--
作者：
Gupta SC;Prasad S;Kim JH;Patchva S;Webb LJ;Priyadarsini IK;Aggarwal BB
姜黄素(二阿魏酰甲烷)是姜黄中的有效成分，具有抗炎、抗氧化、化学预防、化学增敏和放射增敏等多种活性。姜黄素的多效性来源于其复杂的分子结构和化学结构，以及影响多个信号分子的能力。姜黄素通过多种作用力直接与多种信号分子结合，如炎症分子、细胞存活蛋白、蛋白激酶、蛋白还原酶、组蛋白乙酰转移酶、组蛋白去乙酰化酶、乙二酸酶I、黄嘌呤氧化酶、蛋白酶体、HIV1整合酶、HIV1蛋白酶、肌浆网钙离子ATPase、DNA甲基转移酶1、FtsZ原丝、载体蛋白和金属离子等。姜黄素还可以直接与DNA和RNA结合。由于其β-二酮部分，姜黄素经历了酮-烯醇互变异构化，这已被报道为有利于直接结合的状态。姜黄素上适合与其他大分子相互作用的官能团包括α，β-不饱和β-二酮部分、β-二酮部分的羰基和烯基、甲氧基和酚羟基以及苯环。各种生物物理手段已经被用来监测姜黄素与其他蛋白质的直接相互作用，包括吸收、荧光、傅里叶变换红外(FTIR)和圆二色(CD)光谱、表面等离子体共振、竞争配体结合、Forster类型荧光共振能量转移(FRET)、放射性标记、定点突变、基质辅助激光解吸/电离飞行时间质谱仪(MALDI-TOF MS)、免疫沉淀、噬菌体展示生物扫描、电子显微镜、1-苯胺基-8-萘磺酸盐(ANS)置换和共定位。分子对接是计算结合亲和力和预测结合位点的最常用的计算工具，也被用来进一步表征姜黄素的结合位点。此外，姜黄素直接与载体蛋白结合的能力提高了它的溶解度和生物利用度。在这篇综述中，我们重点介绍了姜黄素如何直接靶向信号分子，以及结合姜黄素-蛋白质复合体的不同作用力，以及这种相互作用如何影响蛋白质的生物学性质。我们还将讨论姜黄素的各种类似物，旨在结合具有更高亲和力的选择性靶标。
Curcumin (diferuloylmethane), the active ingredient in turmeric (Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities. The pleiotropic activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules. Curcumin has been shown to bind by multiple forces directly to numerous signaling molecules, such as inflammatory molecules, cell survival proteins, protein kinases, protein reductases, histone acetyltransferase, histone deacetylase, glyoxalase I, xanthine oxidase, proteasome, HIV1 integrase, HIV1 protease, sarco (endo) plasmic reticulum Ca2+ ATPase, DNA methyltransferases 1, FtsZ protofilaments, carrier proteins, and metal ions. Curcumin can also bind directly to DNA and RNA. Owing to its β-diketone moiety, curcumin undergoes keto–enol tautomerism that has been reported as a favorable state for direct binding. The functional groups on curcumin found suitable for interaction with other macromolecules include the α, β-unsaturated β-diketone moiety, carbonyl and enolic groups of the β-diketone moiety, methoxy and phenolic hydroxyl groups, and the phenyl rings. Various biophysical tools have been used to monitor direct interaction of curcumin with other proteins, including absorption, fluorescence, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy, surface plasmon resonance, competitive ligand binding, Forster type fluorescence resonance energy transfer (FRET), radiolabeling, site-directed mutagenesis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), immunoprecipitation, phage display biopanning, electron microscopy, 1-anilino-8-naphthalene-sulfonate (ANS) displacement, and co-localization. Molecular docking, the most commonly employed computational tool for calculating binding affinities and predicting binding sites, has also been used to further characterize curcumin’s binding sites. Furthermore, the ability of curcumin to bind directly to carrier proteins improves its solubility and bioavailability. In this review, we focus on how curcumin directly targets signaling molecules, as well as the different forces that bind the curcumin–protein complex and how this interaction affects the biological properties of proteins. We will also discuss various analogues of curcumin designed to bind selective targets with increased affinity.
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影响因子：
5.1
作者：
Awasthi, S;Pandya, U;Ansari, GAS
通讯作者：
Ansari, GAS
DOI：
10.1016/j.biocel.2008.06.010
发表时间：
2009-01
影响因子：
4
作者：
Aggarwal, Bharat B.;Harikumar, Kuzhuvelil B.
通讯作者：
Harikumar, Kuzhuvelil B.
影响因子：
64.8
作者：
Eckstein-Ludwig, U;Webb, RJ;Krishna, S
通讯作者：
Krishna, S
影响因子：
10.2
作者：
Bisht S;Feldmann G;Soni S;Ravi R;Karikar C;Maitra A;Maitra A
通讯作者：
Maitra A
影响因子：
4.1
作者：
Balogun, E;Hoque, M;Motterlini, R
通讯作者：
Motterlini, R