Biochimica et biophysica acta. General subjects最新文献_第4页

Electroporation-derived melanoma extracellular particles activate fibroblasts 电穿孔衍生的黑色素瘤细胞外颗粒可激活成纤维细胞。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-18 DOI: 10.1016/j.bbagen.2024.130723

Anna Choromańska , Urszula Szwedowicz , Anna Szewczyk , Małgorzata Daczewska , Jolanta Saczko , Roksana Kruszakin , Krzysztof J. Pawlik , Dagmara Baczyńska , Julita Kulbacka

Although the pulse electric field (PEF) has been used in electrochemotherapy (ECT) for many years, the kinetics and profile of extracellular particles (EPs) released as a result of reversible electroporation have yet to be studied. It also needs to be clarified whether and how the profile of released EPs depends on the parameters of the applied PEF. The presented studies investigated the effect of EPs released from human melanoma cells after various parameters of reversible electroporation on markers indicating EP-mediated transformation of normal fibroblasts into tumor-associated fibroblasts. The expression levels of the vascular cell adhesion molecule-1 (VCAM-1) and changes in the expression of phosphor-histone H3 (pHH3), a biomarker specific for cells in mitosis, cell viability, and the migration capacity of the studied fibroblast cells, were analyzed. EPs were isolated from two commercial malignant melanoma cell lines previously subjected to reversible electroporation. Human primary fibroblasts (HPFs) were selected for EPs exposure. It was observed that after incubation with melanoma-derived EPs, HPFs showed differences in cell viability, migration capacity, VCAM-1, pHH3, and N-cadherin expression, depending on PEF parameters and the grade of melanoma cells. This study highlights that small extracellular particles (sEPs) from cancer cells can promote metastasis by carrying specific signals that lead to the upregulation of molecules like FAK, MMP-9, and N-cadherin in recipient cells.

尽管脉冲电场（PEF）已在电化学疗法（ECT）中应用多年，但对可逆电穿孔释放的细胞外微粒（EPs）的动力学和概况仍有待研究。此外，还需要澄清释放的 EPs 的形态是否以及如何取决于所应用的 PEF 参数。本研究调查了人类黑色素瘤细胞在不同参数的可逆电穿孔后释放的 EPs 对显示 EP 介导的正常成纤维细胞向肿瘤相关成纤维细胞转化的标志物的影响。研究人员分析了血管细胞粘附分子-1（VCAM-1）的表达水平、有丝分裂期细胞特异性生物标志物磷组蛋白 H3（pHH3）的表达变化、细胞活力以及所研究成纤维细胞的迁移能力。EPs是从两种商业化恶性黑色素瘤细胞系中分离出来的，这些细胞系曾接受过可逆电穿孔。人类原代成纤维细胞（HPFs）被选中用于暴露于 EPs。结果表明，在与黑色素瘤衍生EPs培养后，HPFs在细胞活力、迁移能力、VCAM-1、pHH3和N-cadherin表达方面表现出差异，这取决于PEF参数和黑色素瘤细胞的等级。这项研究强调，癌细胞的小细胞外颗粒（sEPs）可通过携带特定信号促进转移，这些信号可导致受体细胞中FAK、MMP-9和N-cadherin等分子的上调。

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引用次数: 0

Personalized biocorona as disease biomarker: The challenges and opportunities 作为疾病生物标志物的个性化生物传感器：挑战与机遇。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-18 DOI: 10.1016/j.bbagen.2024.130724

Mahtab Jahanshah Talab , Ali Valizadeh , Zahra Tahershamsi , Mohammad Reza Housaindokht , Bijan Ranjbar

It is well known that when nanoparticles interact with biological fluids, a layer of proteins and biological components forms on them. This layer may alter the biological fate and efficiency of the nanomaterial. Recent studies have shown that illness states have a major impact on the structure of the biocorona, sometimes referred to as the “personalized protein corona.” Physiological factors like illness, which impact the proteome and metabolome pattern and result in conformational changes in proteins, give rise to this structure of discrimination in biocorona decoration. Improving the efficiency of precise platforms for developing new molecular biomarkers for accurate illness diagnosis is vitally necessary. The biocorona pattern's discrimination may be a diagnostic tool for designing biosensors. As a result, in this review, we summarize the most current studies on the relationship between physiological conditions and the variety of biocorona patterns that influence the biological responses of nanosystems. The biocorona pattern's flexibility may provide new research directions and be utilized to create nanoparticle-based therapeutic and diagnostic products suited to certain physiological situations.

众所周知，当纳米粒子与生物液体相互作用时，会在其上形成一层蛋白质和生物成分层。这一层可能会改变纳米材料的生物学命运和效率。最近的研究表明，疾病状态对生物冠层（有时称为 "个性化蛋白质冠层"）的结构有重大影响。疾病等生理因素会影响蛋白质组和代谢组模式，导致蛋白质构象发生变化，从而在生物电晕装饰中产生这种辨别结构。提高精确平台的效率，为准确诊断疾病开发新的分子生物标志物是非常必要的。生物电晕图案的辨别力可以作为设计生物传感器的诊断工具。因此，在这篇综述中，我们总结了有关生理条件与影响纳米系统生物反应的各种生物电晕模式之间关系的最新研究。生物电晕模式的灵活性可能会为我们提供新的研究方向，并可利用它创造出适合特定生理情况的基于纳米粒子的治疗和诊断产品。

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引用次数: 0

FAHFA promotes intracellular calcium signaling via activating the fat taste receptor, CD36 and Src protein kinases in mice taste bud cells FAHFA 通过激活小鼠味蕾细胞中的脂肪味觉受体、CD36 和 Src 蛋白激酶促进细胞内钙信号转导。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-18 DOI: 10.1016/j.bbagen.2024.130722

Karthi Muthuswamy , Keerthana Vasanthakumar , Prabha Panneerselvan , Lokesh Thangamani , Vasanth Krishnan , Shanmughavel Piramanayagam , Selvakumar Subramaniam

Two lipid sensors, CD36 and GPR120, are crucial for the orosensory detection of fat taste and for mediating fat preference. However, the mechanism by which endogenous lipid (FAHFA) binds to CD36 to initiate intracellular signaling remains unexplained. Hence, the primary objective of this study is to investigate the binding mechanism of FAHFA to CD36 and its role in isolated mouse taste bud cells (mTBCs). The Schrodinger platform was used to assess the molecular dynamics of protein and ligand interactions, and an in vitro experiment was used to validate the findings. Based on the docking score of the ligand, the molecular mechanistic activities of the targeted complexes, CD36–5-POHSA (−8.2 kcal/mol), were investigated using the dynamic simulation. In comparison to linoleic acid (LA), POHSA rapidly increased [Ca²⁺]i via acting on CD36, and 5-POHSA treatment in mTBCs activated src-kinase at 20 μM. CD36 siRNA transfection in TBCs downregulate the CD36 protein expression as well as [Ca²⁺]i flux. This study suggests that 5-POHSA may help combat taste abnormalities and the adverse effects of obesity by binding to the lingual CD36 receptor and activating the tongue-brain axis.

CD36和GPR120这两个脂质传感器对于脂肪味道的口感检测和脂肪偏好的介导至关重要。然而，内源性脂质（FAHFA）与 CD36 结合以启动细胞内信号传导的机制仍未解释。因此，本研究的主要目的是探讨 FAHFA 与 CD36 的结合机制及其在离体小鼠味蕾细胞（mTBCs）中的作用。本研究利用薛定谔平台评估了蛋白质和配体相互作用的分子动力学，并利用体外实验验证了研究结果。根据配体的对接得分，利用动态模拟研究了目标复合物 CD36-5-POHSA（-8.2 kcal/mol）的分子机理活性。与亚油酸（LA）相比，POHSA 可通过作用于 CD36 快速增加[Ca2+]i，5-POHSA 在 20 μM 时可激活 mTBC 中的 src 激酶。转染 CD36 siRNA 的 TBCs 可下调 CD36 蛋白表达和[Ca2+]i 通量。这项研究表明，5-POHSA 可通过与舌 CD36 受体结合并激活舌脑轴，帮助对抗味觉异常和肥胖的不良影响。

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引用次数: 0

VotePLMs-AFP: Identification of antifreeze proteins using transformer-embedding features and ensemble learning VotePLMs-AFP：利用变压器嵌入特征和集合学习识别抗冻蛋白

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-18 DOI: 10.1016/j.bbagen.2024.130721

Dawei Qi, Taigang Liu

Antifreeze proteins (AFPs) are a unique class of biomolecules capable of protecting other proteins, cell membranes, and cellular structures within organisms from damage caused by freezing conditions. Given the significance of AFPs in various domains such as biotechnology, agriculture, and medicine, several machine learning methods have been developed to identify AFPs. However, due to the complexity and diversity of AFPs, the predictive performance of existing methods is limited. Therefore, there is an urgent need to develop an efficient and rapid computational method for accurately predicting AFPs. In this study, we proposed a novel predictor based on transformer-embedding features and ensemble learning for the identification of AFPs, termed VotePLMs-AFP. Firstly, three types of feature descriptors were extracted from pre-trained protein language models (PLMs) during the feature extraction process. Subsequently, we analyzed six combinations generated by these three embeddings to explore the optimal feature set, which was input into the soft voting-based ensemble learning classifier for the identification of AFPs. Finally, we evaluated the model on the two benchmark datasets. The experimental results show that our model achieves high prediction accuracy in 10-fold cross-validation (CV) and independent set testing, outperforming existing state-of-the-art methods. Therefore, our model could serve as an effective tool for predicting AFPs.

抗冻蛋白（AFPs）是一类独特的生物大分子，能够保护生物体内的其他蛋白质、细胞膜和细胞结构免受冷冻条件的破坏。鉴于抗冻蛋白在生物技术、农业和医学等各个领域的重要性，人们开发了多种机器学习方法来识别抗冻蛋白。然而，由于 AFP 的复杂性和多样性，现有方法的预测性能有限。因此，迫切需要开发一种高效、快速的计算方法来准确预测 AFPs。在这项研究中，我们提出了一种基于变压器嵌入特征和集合学习的新型预测方法，用于识别 AFP，称为 VotePLMs-AFP。首先，在特征提取过程中，我们从预先训练好的蛋白质语言模型（PLMs）中提取了三种类型的特征描述符。随后，我们分析了由这三种嵌入产生的六种组合，以探索最佳特征集，并将其输入基于软投票的集合学习分类器，用于识别 AFP。最后，我们在两个基准数据集上对模型进行了评估。实验结果表明，我们的模型在 10 倍交叉验证（CV）和独立集测试中都达到了很高的预测准确率，优于现有的先进方法。因此，我们的模型可以作为预测 AFP 的有效工具。

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引用次数: 0

Supplementation with ions enhances the efficiency of nucleic acid delivery with cell-penetrating peptides 补充离子可提高细胞穿透肽递送核酸的效率。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-05 DOI: 10.1016/j.bbagen.2024.130719

İrem Ilgın Gümüşoğlu , Maria Maloverjan , Ly Porosk, Margus Pooga

The successful delivery of therapeutic nucleic acids (NAs) into eukaryotic cells is essential for numerous biomedical applications, including gene therapy, gene silencing, and genome editing. Cell-penetrating peptides (CPPs) have claimed significant attention as delivery vehicles due to their inherent ability to penetrate cellular membranes and efficiently transport cargo, including NAs, into the cells. However, further optimization and a deeper understanding of underlying mechanisms are necessary for such transfection methods. Previous studies have demonstrated that Ca²⁺ ions can significantly enhance NA delivery efficiency when included in transfection media or CPP/NA nanoparticles during preparation. Similar effects have been observed for Mg²⁺, but the impact of other ions in this context has not been thoroughly investigated. In this study, we supplemented the CPP/NA formulations with various inorganic biocompatible ions by introducing solutions of the respective salts to colloidal nanoparticles at the preparation stage. Our results indicated that supplementing the CPP/NA formulations with certain salt solutions enhanced the biological effect achieved with NAs while also influencing nanoparticle size, surface charge, complexation stability, and, to some extent, the internalization route. Our findings offer valuable insights for optimizing the formation of CPP nanoparticles to improve NA delivery efficiency.

成功地将治疗性核酸（NAs）输送到真核细胞中对于基因治疗、基因沉默和基因组编辑等众多生物医学应用至关重要。细胞穿透肽（CPPs）具有穿透细胞膜并将货物（包括核酸）高效转运到细胞内的固有能力，因此作为转运载体备受关注。然而，这种转染方法还需要进一步优化和深入了解其潜在机制。先前的研究表明，在转染介质或 CPP/NA 纳米颗粒制备过程中加入 Ca2+ 离子可显著提高 NA 的输送效率。在 Mg2+ 中也观察到了类似的效果，但其他离子在这方面的影响尚未得到深入研究。在本研究中，我们通过在制备阶段向胶体纳米粒子中引入相应的盐溶液，在 CPP/NA 配方中补充了各种无机生物相容性离子。结果表明，在 CPP/NA 制剂中添加某些盐溶液可增强 NAs 的生物效应，同时还可影响纳米粒子的大小、表面电荷、复合物稳定性，并在一定程度上影响内化途径。我们的研究结果为优化 CPP 纳米粒子的形成以提高 NA 的递送效率提供了宝贵的见解。

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引用次数: 0

Characterization of the intracellular polyphosphate granules of the phototrophic green sulfur bacterium Chlorobaculum tepidum 光营养型绿色硫细菌 Chlorobaculum tepidum 细胞内聚磷酸盐颗粒的特征。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-05 DOI: 10.1016/j.bbagen.2024.130718

Alexandros Lyratzakis, Michail Kalogerakis, Katerina Polymerou, Apostolos Spyros, Georgios Tsiotis

The ability to generate polyphosphate (polyP) granules is important for survival for bacteria during resistance to diverse environmental stresses, however the genesis of polyP granules is poorly understood. Chlorobaculum tepidum (Cba tepidum) is a thermophilic green sulfur anoxygenic phototrophic bacterium which uses reduced sulfur compounds as electron donors. The presence of electron rich granules inside the Cba tepidum was reported, but no further information was provided. In this work we used cell thin sections at three different time points of cultivation to observe the biogenesis of the inclusions over time, and the in cell total phosphate concentration was monitored over time as well. Furthermore, the elemental analysis (EDS) of the electron rich inclusions showed the presence of phosphorus and oxygen. The existence of polyphosphate was demonstrated by ³¹P NMR spectroscopy of cell lysates. Finally, we show that the biogenesis of the phosphorus granules correlates with an abundance of proteins that are closely related to polyphosphate metabolism.

产生聚磷酸盐（polyP）颗粒的能力对细菌在抵抗各种环境压力时的生存非常重要，但人们对聚磷酸盐颗粒的成因却知之甚少。Chlorobaculum tepidum（Cba tepidum）是一种嗜热的绿色含硫无氧光营养细菌，它使用还原硫化合物作为电子供体。有报道称 Cba tepidum 内部存在富电子颗粒，但未提供更多信息。在这项工作中，我们使用了三个不同培养时间点的细胞薄片来观察包涵体随着时间推移的生物生成过程，同时还监测了细胞内磷酸盐的总浓度。此外，富电子包涵体的元素分析（EDS）显示了磷和氧的存在。细胞裂解物的 31P NMR 光谱证明了多磷酸盐的存在。最后，我们表明磷颗粒的生物生成与与多磷酸盐代谢密切相关的蛋白质的丰富程度相关。

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引用次数: 0

FCS videos: Fluorescence correlation spectroscopy in space and time FCS 视频：时空荧光相关光谱。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-09-28 DOI: 10.1016/j.bbagen.2024.130716

Thorsten Wohland , Shao Ren Sim , Marc Demoustier , Shambhavi Pandey , Rutuparna Kulkarni , Daniel Aik

Fluorescence Correlation Spectroscopy (FCS), invented more than 50 years ago is a widely used tool providing information on molecular processes in a variety of samples from materials to life sciences. In the last two decades FCS was multiplexed and ultimately made into an imaging technique that provided maps of molecular parameters over whole sample cross-section. However, it was still limited by a measurement time on the order of minutes. With the improvement of FCS time resolution to seconds using deep learning, we extend here FCS to so-called FCS videos that can provide information how the molecular parameters determined by Imaging FCS change in space and time. This opens up new possibilities for the investigation of molecular processes. Here, we demonstrate the feasibility of the approach and show FCS video applications to lipid bilayers and cell membranes.

荧光相关光谱（FCS）发明于 50 多年前，是一种广泛应用的工具，可提供从材料到生命科学等各种样品中的分子过程信息。在过去的二十年里，FCS 实现了多路复用，并最终成为一种成像技术，可提供整个样品横截面上的分子参数图。然而，它仍然受限于几分钟的测量时间。随着利用深度学习将 FCS 的时间分辨率提高到秒级，我们在此将 FCS 扩展到所谓的 FCS 视频，它可以提供通过成像 FCS 确定的分子参数在空间和时间上如何变化的信息。这为研究分子过程开辟了新的可能性。在此，我们展示了该方法的可行性，并展示了 FCS 视频在脂质双分子层和细胞膜中的应用。

引用次数: 0

Establishment of the Meyer-Overton correlation in an artificial membrane without protein 在不含蛋白质的人工膜中建立迈耶-奥弗顿相关性。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-09-27 DOI: 10.1016/j.bbagen.2024.130717

Atsushi Matsumoto , Yukifumi Uesono

Background

The potency of anesthetics with various structures increases exponentially with lipophilicity, which is the Meyer-Overton (MO) correlation discovered over 120 years ago. The MO correlation was also observed with various biological effects and chemicals, including alcohols; thus, the correlation represents a fundamental relationship between chemicals and organisms. The MO correlation was explained by the lipid and protein theories, although the principle remains unknown because these are still debating.

Methods

The gentle hydration method was used to form giant unilamellar vesicles (GUVs) consisting of high- and low-melting phospholipids and cholesterol in the presence of n-alcohols (C₂-C₁₂). Confocal fluorescence microscopy was used to determine the percentage of GUVs with domains in relation to the n-alcohol concentrations.

Results

n-Alcohols inhibited the domain formation of GUVs, and the half inhibitory concentration (IC₅₀) in the aqueous phase (C_w) decreased exponentially with increasing chain length (lipophilicity). In contrast, the membrane concentrations (C_m) of alcohols for the inhibition, which is a product of the membrane-water partition coefficient and the IC₅₀ values, remained constant irrespective of the chain length.

Conclusions

The MO correlation is established in GUVs, which supports the lipid theory. When alcohols reach the same critical concentration in the membrane, similar biological effects appear irrespective of the chain length, which is the principle underlying the MO correlation.

General significance

The protein theory states that a highly lipophilic compound targets minor membrane proteins due to the low C_w. However, our lipid theory states that the compound targets various membrane proteins due to the high C_m.

背景：各种结构的麻醉剂的药效随着亲脂性的增加而呈指数增长，这就是 120 多年前发现的迈耶-奥弗顿（MO）相关性。在各种生物效应和化学品（包括酒精）中也观察到了 MO 相关性；因此，这种相关性代表了化学品和生物体之间的一种基本关系。MO 相关性可以用脂质和蛋白质理论来解释，但其原理仍然不明，因为这些理论仍在争论之中：方法：在正丙醇（C2-C12）存在的情况下，使用温和水合法形成由高熔点和低熔点磷脂和胆固醇组成的巨型单拉美拉尔囊泡 (GUV)。结果：正丁醇抑制了 GUV 的结构域形成，水相（Cw）中的半抑制浓度（IC50）随着链长（亲脂性）的增加呈指数下降。与此相反，抑制作用的醇膜浓度（Cm），即膜-水分配系数与 IC50 值的乘积，无论链长多少都保持不变：结论：在 GUV 中建立了 MO 相关性，这支持了脂质理论。当醇在膜中达到相同的临界浓度时，无论链长如何，都会出现相似的生物效应，这就是 MO 相关性的基本原理：一般意义：蛋白质理论认为，高亲脂性化合物由于Cw较低，会针对次要膜蛋白。然而，我们的脂质理论则认为，由于高 Cm，化合物会针对各种膜蛋白。

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引用次数: 0

SecM leader peptide as an allosteric translation inhibitor: a molecular dynamics study 作为异位翻译抑制剂的 SecM 领导肽：分子动力学研究

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-09-26 DOI: 10.1016/j.bbagen.2024.130715

G.I. Makarov, T.M. Makarova

The SecM leader peptide regulates translation of the SecA protein, being a part of the Sec translocase, that reversibly arrests the ribosome. In the present study the structure of the SecM complex with the E. coli A/A,P/P–ribosome was obtained by means of docking and molecular dynamics simulation methods. It has been established that binding of the SecM leader peptide in the nascent peptide exit tunnel leads to a turn of the aminoacylating proline residue away from the C–terminal SecM glycine residue, which is adverse to the peptidyltransferase reaction. Besides, the SecM binding leads to a disturbance of the A–tRNA contacts with the tip of the H38 helix of the 23S rRNA (the A–site finger, ASF) and ribosomal protein uL16. Allosteric interrelation between these events has been proved by a construction of networks of concerted changes in non–covalent interactions throughout the whole ribosome, whereupon the A1614 and A751 residues of the 23S rRNA in the exit tunnel that formed stacking interactions with the SecM residues during the MD simulations, were found to be the principal triggers, inducing crucial alterations in the A–tRNA binding. The allosteric signal from the SecM peptide to the ASF, according to our model, is transmitted through ribosomal protein uL22, and there is reason to believe that this sensor is used not only by the SecM leader peptide, but also by other peptides that cause translation arrest.

SecM 头肽调节 SecA 蛋白的翻译，SecA 蛋白是 Sec 易位酶的一部分，可逆性地抑制核糖体。本研究通过对接和分子动力学模拟方法，获得了 SecM 与大肠杆菌 A/A,P/P-核糖体的复合物结构。研究证实，SecM 头肽在新生肽出口隧道中的结合会导致氨基酰化脯氨酸残基转向远离 C 端 SecM 甘氨酸残基，从而不利于肽基转移酶反应。此外，SecM 的结合导致 A-tRNA 与 23S rRNA 的 H38 螺旋顶端（A 位点指，ASF）和核糖体蛋白 uL16 的接触受到干扰。通过构建整个核糖体非共价相互作用的协同变化网络，证明了这些事件之间的异化作用相互关系。在 MD 模拟过程中，23S rRNA 出口隧道中与 SecM 残基形成堆叠相互作用的 A1614 和 A751 残基被发现是主要的触发器，诱发了 A-tRNA 结合的关键变化。根据我们的模型，从 SecM 肽到 ASF 的异构信号是通过核糖体蛋白 uL22 传递的，因此有理由相信，不仅 SecM 头肽，而且其他导致翻译停止的肽也会使用这种传感器。

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引用次数: 0

Multispectral and molecular simulation of the interaction of human α1-acid glycoprotein with palbociclib 人类α1-酸性糖蛋白与帕博西尼相互作用的多光谱和分子模拟。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-09-21 DOI: 10.1016/j.bbagen.2024.130712

Shao-Liang Jiang , Yu-Ting Wu , Wang-Cai Chen , Jia-Ping Huang , Dong Chen , Li Li , Liang Han , Jie-Hua Shi

Palbociclib, a selective CDK4/6 inhibitor with potent anti-tumor effects, was investigated for its interaction with human α1-acid glycoprotein (HAG). Spectral analysis revealed that palbociclib forms a ground state complex with HAG, exhibiting binding constant (K_b) of 10⁴ M⁻¹ at the used temperature range. The interaction between the two was determined to be driven mainly by hydrogen bonding and hydrophobic forces. Multispectral studies indicated that the bound palbociclib altered the secondary structure of HAG and reduced polarity around Trp and Tyr amino acids. And, molecular docking and dynamics simulations verified the experimental findings. Finally, most of the metal ions present in plasma, such as K⁺, Cu²⁺, Ca²⁺, Mg²⁺, Ni²⁺, Fe³⁺, and Co²⁺, are detrimental to the binding of palbociclib to HAG, with the exception of Zn²⁺, which is favorable.

帕博西尼（Palbociclib）是一种选择性CDK4/6抑制剂，具有很强的抗肿瘤作用，研究人员考察了它与人类α1-酸糖蛋白（HAG）的相互作用。光谱分析显示，palbociclib 与 HAG 形成基态复合物，在所用温度范围内的结合常数（Kb）为 104 M-1。二者之间的相互作用主要由氢键和疏水作用力驱动。多光谱研究表明，结合后的帕博西尼改变了 HAG 的二级结构，降低了 Trp 和 Tyr 氨基酸周围的极性。分子对接和动力学模拟也验证了实验结果。最后，血浆中存在的大多数金属离子，如 K+、Cu2+、Ca2+、Mg2+、Ni2+、Fe3+ 和 Co2+，都不利于 palbociclib 与 HAG 的结合，只有 Zn2+ 有利。

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引用次数: 0