BIOCHEMISTRY生物化学
BIOCHEMISTRY(英文缩写 BIOCHEMISTRY-US),ISSN 0006-2960,eISSN 1520-4995,中文译名:生物化学 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-28 至 2026-09-28，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 3.321 | Q3 |
| 2022 | 2.900 | Q3 |
| 2023 | 2.900 | Q3 |
| 2024 | 3.000 | Q3 |
| 2025 | 2.700 | Q3 |
BIOCHEMISTRY 最新收录文献
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1. Molecular Rewiring and Compensatory Mechanisms Sustain DNA Recognition in the Mutant ZTA Transcription Factor: Insights from Molecular Dynamics Simulations.
PMID:日期:2026-09-16Protein-DNA complexes are stabilized by various interactions through an interaction network between protein and DNA. Any change in the system─whether through mutations in protein/DNA, external factors, or protein conformational transitions─can alter the interaction network, affecting structural and functional aspects. Employing all-atom classical molecular dynamics, we investigated how the interaction network in ZTA-DNA is rewired, while key arginine residues in ZTA are mutated to oppositely charged glutamic acids. Using the MM/PBSA technique, we computed per-residue binding energies and correlated them with structural features. A detailed mechanistic study shows that mutations in key arginine residues form new interactions either around the mutation site and/or in the other ZTA monomer. Through load-sharing system attempts to counterbalance the interaction load, leading to reorganization of the existing interaction network. From single- to double-site mutations, the complex partially maintains its structural stability through additional interactions formed by lysine, particularly K178, while multisite mutations cannot sustain its structural stability, leading to system destabilization. Despite inherent structural symmetry in ZTA, an asymmetric monomer contribution is observed upon mutation. The binding affinity of the ZTA-DNA complex shows a good correlation with structural and interaction features, following the trend A > E ≈ D > C ≫ B. Overall, our rigorous mechanistic study provides deeper insights into the interaction network reorganization mechanism in the ZTA-DNA system. Since ZTA is a key factor in the Epstein-Barr virus (EBV), this study will be central to understanding DNA recognition and developing drug therapeutics targeting viral transcription factors in EBV.
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3. The Photocycle of the Red Light-Sensitive Plant-like Cryptochrome CryP from Phaeodactylum tricornutum.
PMID:日期:2026-09-01Cryptochromes act as photoreceptors in diverse organisms and bind flavin adenine dinucleotide (FAD) as a chromophore. The plant-like cryptochrome CryP from the diatom Phaeodactylum tricornutum regulates in vivo the expression of light-harvesting proteins in response to blue light. CryP carries, in addition, 5,10-methenyltetrahydrofolate (MTHF) for light capturing. In contrast to most other cryptochromes, FAD in CryP is present as a stable flavin neutral radical in the dark, which undergoes a photoreduction to form the fully reduced state in the light. Here, we demonstrate by applying nanosecond-time-resolved UV-vis spectroscopy that the flavin neutral radical is photoreduced within 100 ns to the fully reduced state and subsequently recovers very fast with a time constant of 1.4 ms in the absence of reducing agents or in the presence of 1 mM dithiothreitol. Despite its short lifetime, the transient light state is sufficient to induce homo-oligomerization of CryP as shown by light-dependent size exclusion chromatography. A long-lived fully reduced flavin is only formed in the presence of external reducing agents by a second pathway that is lost after a single full conversion, likely by degradation. Then, the recovery to the neutral radical state takes hours with a time constant of 40 min. Moreover, we validate the existence of energy transfer between the two chromophores depending on the flavin redox state using fluorescence spectroscopy. We propose a detailed mechanism for the photocycle of CryP, highlighting the contribution of two separate reduction pathways.
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4. Chemical Pathway-Dependent Structural Reorganization at a Hinge Microenvironment in the AcrA Adaptor Protein.
PMID:日期:2026-09-01Adaptor protein AcrA plays a central role in the assembly and function of tripartite multidrug efflux pumps in Gram-negative bacteria, yet how its structural organization responds to coupled chemical perturbations rather than solely to equilibrium conditions remains unclear. Residues near His285 define a hinge microenvironment linking the lipoyl and β-barrel domains, suggesting a site for chemically sensitive structural modulation. Here, site-directed spin labeling combined with continuous-wave electron paramagnetic resonance spectroscopy was used to examine AcrA under an Mg2+-driven perturbation that simultaneously alters proton availability. Mg2+ addition produced spectral broadening at residue 62 that was fully reversed by spin dilution, indicating increased interspin proximity without changes in intrinsic side-chain dynamics. In contrast, direct acidification to a comparable bulk pH in the absence of Mg2+ did not reproduce this behavior. Structural mapping places residue 62 in proximity to the His285-centered hinge region, suggesting that coupled changes in protonation and metal coordination bias local interaction networks and modulate interdomain organization. These findings demonstrate that equivalent bulk conditions can mask distinct molecular states and identify chemical pathways as an important determinant of AcrA structural dynamics.
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5. Improved Protein Semi-Synthesis Enables Biophysical Studies of Thioamide Destabilization of β-Sheet Interactions.
PMID:日期:2026-09-01Thioamides are natural post-translational modifications of the peptide backbone and can be introduced synthetically to probe protein folding or functionalize peptides for translational applications. In this work, we demonstrate that thioamide-containing peptides with C-terminal thioesters can be efficiently generated using Knorr pyrazole activation and used in subsequent native chemical ligation reactions to generate thioamide-containing proteins. We compare this method to acyl azide activation and find that both routes provide similar yields. We also investigate ultrasound-mediated desulfurization of the ligation site cysteine for potential advantages over chemical radical initiators. Scaling up our syntheses allows us to study thioamide perturbations to the β-sheet region of the B1 domain of protein G (GB1) as well as β-strand interactions in amyloid fibrils of the Parkinson's disease protein α-synuclein. In both contexts, we observe dramatic destabilization of the β-sheet networks, manifested in decreased GB1 thermal stability and altered folding and slowed aggregation of α-synuclein. These findings illustrate the impact that a single atom substitution can have on cooperative hydrogen-bonding networks and prompt future study of both systems.
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6. Recognition of Single-Strand-Duplex Junctions in RNA Using Peptide Nucleic Acids That Form Watson-Crick and Hoogsteen Hydrogen Bond.
PMID:日期:2026-09-01Sequence-specific recognition of complex, folded RNA structures is a highly desirable yet formidable goal. The present study explored nucleobase-modified peptide nucleic acids (PNAs) as ligands that bind and recognize junctions between single- and double-stranded RNA via Watson-Crick and Hoogsteen hydrogen bonding, respectively. The results showed that these hybrid PNAs exhibited strong affinity for RNA junctions and transitioned from duplex to triplex binding modes without additional modification. However, depending on the sequence context, extending the PNA's backbone at the transition site could yield a slight improvement in binding affinity. The overall binding affinity was modest and comparable to that of triplex-only binding. The duplex-triplex binding mode exhibited relatively low sensitivity to mismatches adjacent to the transition site, suggesting that the transition might be dynamic and not well organized. Overall, the results demonstrated PNA's ability to recognize single-double-strand junctions in RNA; however, the modest stability and specificity might limit this binding mode to specific cases where simpler duplex or triplex binding modes are not feasible.
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7. A Molecular Mechanistic Deep Dive into 14-3-3 Molecular Glue Cooperativity.
PMID:日期:2026-09-01Molecular glues (MGs) stabilize protein-protein interactions (PPIs) through interactions at composite binding interfaces, thereby promoting cooperative ternary complex formation. For hub proteins that engage in multiple PPIs with widely varying intrinsic affinities, the interplay between binary PPI affinity and MG cooperativity is therefore a key determinant of selective stabilization. Here, we use the multiclient 14-3-3 scaffold protein as a model system to systematically dissect the relationship between binary 14-3-3/client affinity (KDI) and MG-induced cooperativity (α). Client peptide affinity was systematically tuned by modifying residues N-terminal to the phosphorylated 14-3-3 binding motif while preserving the C-terminal composite interface required for MG recognition. Using a combination of biophysical techniques and protein crystallography, we show that changes in KDI alter the thermodynamic and kinetic parameters of both binary and ternary complex formation, but do not affect MG cooperativity. This principle was observed for the noncovalent MG fusicoccin-A as well as covalent MGs targeting 14-3-3σ/client complexes. Competitive binding experiments and thermodynamic modeling further revealed that, although α is independent of KDI, the interplay between KDI, MG affinity (KDII), and cooperativity determines which PPIs are preferentially stabilized in a multiclient environment. Together, these findings establish cooperativity, intrinsic PPI affinity, and MG affinity as key parameters governing MG activity and selectivity, providing a framework for the rational design of MGs targeting hub protein interactomes.
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8. Creating New Access Points for Strategic Synthase Engineering: Ethane Thioester Analogs as Truncated Coenzyme A Building Blocks Unlock Expanded Acyl Carrier Protein Loading Capabilities.
PMID:日期:2026-09-01Strategic engineering of natural product biosynthetic pathways through the incorporation of alternative, tunable carbon-based building blocks represents a promising approach for accessing medicinally relevant molecules. However, efforts toward this goal have been hindered by the substrate specificity of component enzymes. In type I and type II fatty acid synthases (FASs) and polyketide synthases (PKSs), the acyltransferase (AT) selects a specific malonyl-based coenzyme A (CoA) building block and transfers it onto the acyl carrier protein (ACP) for subsequent processing. Inspired by the observation that some ACPs can bypass the AT and "self-acylate", we herein explored the tolerance of FAS and PKS ACPs to load both a variety of CoA substrates and ethane thioester (ET) analogs serving as truncated CoA building blocks. We observe that the Escherichia coli (E. coli) AT, FabD, can load and transfer methylmalonyl-CoA (mm-CoA) and malonyl-CoA (m-CoA) onto three ACPs: the type II Streptomyces coelicolor actinorhodin PKS ACP (ActACP), the E. coli type II FAS ACP (AcpP), and the type I Saccharopolyspora erythraea 6-deoxyerythronolide B PKS ACP6 (DEBS ACP6). Synthesized ET analogs of mm-CoA and m-CoA were loaded onto all three ACPs through FabD-assisted acylation. Additionally, both in the presence and absence of FabD, ACPs could be acylated with ET analogs of fluoromalonyl-, succinyl-, and glutaryl- building blocks. Overall, this work pushes the limits of ACP substrate loading, revealing new complexity in carbon-based building block selection and establishing foundations for novel routes toward diverse functional group incorporation in FAS/PKS biosynthetic pathways.
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9. Designed NIR-I Emissive and Selective G-Quadruplex DNA Binder with Altered Organelle Specificity.
PMID:日期:2026-09-01In this work, we report the discovery of a G-quadruplex DNA-selective and near-infrared (NIR-I) emissive G-quadruplex binder derived from a known styryl-quinolinium-based compound. This molecule is unique in its class, with an emission wavelength above 800 nm, and displays selective G-quadruplex binding. Among the synthesized molecules, compound 2 emerged as a selective and the best G-quadruplex binder through comparative studies and exhibited strong thermal stabilization on Pu22 G-quadruplex with a ΔTm of 21.7 °C (at a 1:3 DNA to ligand ratio). G-quadruplex DNA-binding studies showed that thermal stabilization was topology-dependent. CD, UV-vis, and docking studies were performed to confirm the binding of these compounds to the different G-quadruplexes. Solution NMR studies confirmed the binding of compound 2 to the Pu22 G-quadruplex DNA. Cell-based studies showed that compound 2 was significantly cytotoxic to MCF-7 cancer cells and was readily taken up by the cells. However, cell internalization studies showed contrasting changes in the internalization properties, with compound 2 displaying a significant population on the nuclear periphery, which was altogether different from its parent compound 1, which did not show such changes.
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10. Adductome-Based Identification of Novel Oxidized Phospholipid-Lysine Adducts Formed in Low-Density Lipoprotein.
PMID:日期:2026-09-01The oxidative modification of low-density lipoprotein (LDL) is involved in the generation of lipid peroxidation-derived electrophilic aldehydes, which covalently react with apolipoprotein B-100 to form various adducts. Although the oxidative modification of LDL is critical in the pathogenesis of atherosclerosis, the structural properties of adducts in oxidized LDL (oxLDL) remain unclear. Thus, we aimed to characterize oxLDL using the adductome approach, a comprehensive mass spectrometry-based analysis designed to detect specific product ions from positively ionized oxidized phosphatidylcholine (oxPC) adducts. The amounts of several adducts, including four major oxPC-lysine (oxPC-Lys) adducts, prominently increased when LDL was oxidized with Cu2+. Analysis of the synthetic adduct candidates through mass spectrometry revealed two oxPC-Lys Schiff base adducts and two novel oxPC-Lys amide-type adducts as the major lysine adducts in oxLDL. The oxPC-Lys Schiff base adducts could be transformed into stable amide-type adducts during LDL oxidation. The amounts of oxPC-Lys adducts were significantly higher in the sera of hyperlipidemic mice than in the sera of control mice. The recognition of oxPC-Lys adducts by macrophages suggested that these adducts were involved in the phagocytosis of oxLDL by macrophages. These findings provide insights into the structural properties of lipoproteins modified under oxidative stress and their biological implications. Moreover, this study is the first to identify and quantify oxPC-Lys amide-type adducts in vitro and in vivo.