Article
Biochemistry & Molecular Biology
Yixi Zhang, Zhiwei Shao, Yanqing Gao, Boming Fan, Jie Yang, Xi Chen, Xin Zhao, Qiyuan Shao, Weizhen Zhang, Chulei Cao, Hehua Liu, Jianhua Gan
Summary: Infection of human parvovirus B19 can lead to various diseases, and the NS1_Nuc protein plays a crucial role in viral DNA replication through its unique binding mode with single-stranded DNA.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Xiaoman Jiang, Yang Liu, Qi Liu, Lixin Ma
Summary: This study discovered three active prokaryotic Argonautes (pAgos) with about 50% sequence identity to KmAgo, which have typical DNA-guided DNA target cleavage ability. Among them, RsuAgo from Rummeliibacillus suwonensis was mainly explored for its ability to cleave both DNA and RNA targets, especially with short guide DNAs in the range of 16-20 nt. RsuAgo-mediated RNA target cleavage showed a preference for a guide strand with a 5'-terminal A residue. Furthermore, RsuAgo was found to be able to cleave double-stranded DNA in a low-salt buffer at 37 degrees C, providing a new tool for DNA and RNA manipulation at moderate temperatures.
Article
Biochemistry & Molecular Biology
Yu-Mei Chen, Yu -Can Liu, Jin-Quan Wang, Guang-Chuan Ou, Xiao-Feng Wang, Shu-Qin Gao, Ke-Jie Du, Ying-Wu Lin
Summary: Four copper(II) complexes strongly interact with DNA through partial intercalation and cleave DNA through the generation of singlet oxygen (1O2). In vitro experiments show that these complexes exhibit significant anticancer activity and induce apoptosis in HeLa cells as demonstrated by AO/EB staining.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Monika Janczarek
Summary: Ros/MucR is a widespread family of bacterial zinc-finger-containing proteins that integrate multiple functions in cells, such as symbiosis, virulence, transcription regulation, and motility. They act as repressors through oligomerization and binding to target promoters, similar to xenogeneic silencers in other lineages. The prokaryotic zinc-finger domain exhibits unique structural and functional features and is believed to have originated in alpha-Proteobacteria.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biology
Abdurrahman Pharmacy Yusuf, Murtala Bello Abubakar, Ibrahim Malami, Kasimu Ghandi Ibrahim, Bilyaminu Abubakar, Muhammad Bashir Bello, Naeem Qusty, Sara T. Elazab, Mustapha Umar Imam, Athanasios Alexiou, Gaber El-Saber Batiha
Summary: Zinc was established more than half a century ago as an essential micronutrient for normal human physiology, with around 10% of the human proteome potentially binding zinc. Proteins with zinc-binding domains play key roles in epigenetic modifications, such as DNA methylation and histone modifications, regulating transcription under physiological and pathological conditions. Zinc metalloproteins in epigenetics, mainly zinc metalloenzymes and zinc finger proteins, interact as writers, erasers, readers, editors, and feeders to maintain the epigenome's functioning.
Article
Biochemistry & Molecular Biology
Hephzibah Cathryn R., George Priya Doss C.
Summary: In this study, the effect of mutations on P53 protein was investigated using molecular dynamics simulation. The results showed that the mutations led to loss of hydrogen bonds between DNA binding bases and caused significant movements of the zinc-binding domain.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Genetics & Heredity
Mingxiang Zhang, Jaelyn Z. Current, Heather L. Chaney, Jianbo Yao
Summary: This study identified a novel DNA binding element of the maternal effect gene ZNFO and determined the key nucleotides required for specific binding. The interaction between ZNFO and its DNA binding element was confirmed to be essential for its repressive function through a luciferase-based reporter assay.
Article
Genetics & Heredity
Mingxiang Zhang, Jaelyn Z. Current, Heather L. Chaney, Jianbo Yao
Summary: Maternal effect genes play critical roles in oocyte competence, with the newly identified gene ZNFO playing an important role in early embryonic development in cattle. The study identified the DNA binding element of ZNFO and confirmed its essential role in early embryonic development through interaction with specific nucleotides.
Article
Pharmacology & Pharmacy
Xixi Zhou, Bingye Xue, Sebastian Medina, Scott W. Burchiel, Ke Jian Liu
Summary: The study reveals that U interacts directly with the DNA repair protein PARP-1, resulting in the release of zinc ions from the zinc finger motif and loss of DNA binding activity. However, U does not directly compete with zinc ions in the zinc finger motif and does not show thermodynamic advantages. Furthermore, zinc-bound PARP-1 zinc fingers are insensitive to U treatment, but U binding can be partially replaced by zinc.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Engineering, Biomedical
Pedro Silva-Pinheiro, Christian D. Mutti, Lindsey Van Haute, Christopher A. Powell, Pavel A. Nash, Keira Turner, Michal Minczuk
Summary: The study developed a DNA editor called MitoKO, which can precisely eliminate each protein-coding gene in the mouse mitochondrial genome. MitoKO was used to generate knockout cells with high homoplasmy levels in vitro and a mouse model with high heteroplasmy levels and no off-target edits. This tool will aid in the comprehensive investigation of mtDNA-related pathways and the creation of clinically relevant in vivo models of mtDNA dysfunction.
NATURE BIOMEDICAL ENGINEERING
(2023)
Article
Chemistry, Medicinal
Mark Berney, Manav T. Manoj, Ellen M. Fay, Joanna F. McGouran
Summary: Certain cancers upregulate DNA interstrand crosslink repair pathways, contributing to resistance to chemotherapy drugs and poor prognoses. Inhibiting enzymes involved in interstrand crosslink repair is a promising strategy for improving cancer treatment efficacy. This study aimed to develop more effective SNM1A inhibitors by exploiting interactions with the phosphate-binding pocket adjacent to the enzyme's active site. The incorporation of a 5'-phosphate dramatically increased the potency of the inhibitors.
Article
Biochemistry & Molecular Biology
Justin R. McNally, Amanda M. Ames, Suzanne J. Admiraal, Patrick J. O'Brien
Summary: Double-strand DNA breaks (DSBs) are harmful to cells, and improper repair may lead to chromosome abnormalities and cancer progression. While DNA ligases III and IV (LIG3, LIG4) have been traditionally attributed to DSB repair in mammals, recent evidence suggests that DNA ligase I (LIG1) can compensate for their loss through its intrinsic end-joining (EJ) activity. In this study, researchers compared the EJ activity of LIG1 and LIG3 using in vitro biochemical assays. They found that LIG1 joins blunt-end and 3'-overhang-containing DNA substrates with similar efficiency to LIG3, but joins 5'-overhang-containing DNA substrates about 20-fold less efficiently. Additionally, LIG1's EJ activity is compromised at physiological levels of Mg2+, but can be restored by increasing molecular crowding. In contrast, LIG3 efficiently catalyzes EJ reactions at physiological levels of Mg2+ regardless of molecular crowding. These findings shed new light on the mechanisms of alternative nonhomologous EJ.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yao Dong, Yu-Mei Chen, Xiang-Jun Kong, Shu-Qin Gao, Jia-Jia Lang, Ke-Jie Du, Ying-Wu Lin
Summary: Heme proteins have shown promising potential as artificial metalloenzymes for catalyzing various reactions. In this study, reconstitution of myoglobin with sodium copper cholorophyllin resulted in a new artificial enzyme CuCP-L29E Mb, which exhibited hydrolytic DNA cleavage activity independently of O-2. The DNA cleavage activity of CuCP-L29E Mb was effectively promoted by Mg2+ ions, whereas the wild-type Mb reconstituted with CuCP showed no DNA cleavage activity. This study highlights the critical role of Mg2+ ions and the Glu29 ligand in the nuclease activity of CuCP-L29E Mb, suggesting potential applications for the artificial nuclease in the future.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Robert J. Charman, Neil M. Kad
Summary: This study utilizes high-speed interferometric scattering microscopy and surface-bound DNA assay to uncover the early damage detection mechanism of UvrA. It reveals that the interaction between UvrA and DNA occurs in two phases, with a faster search state allowing UvrA to explore 99% of the E. coli genome within a single division cycle.
Article
Biochemistry & Molecular Biology
Jingwen Song, Syed Nabeel-Shah, Shuye Pu, Hyunmin Lee, Ulrich Braunschweig, Zuyao Ni, Nujhat Ahmed, Edyta Marcon, Guoqing Zhong, Debashish Ray, Kevin C. H. Ha, Xinghua Guo, Zhaolei Zhang, Timothy R. Hughes, Benjamin J. Blencowe, Jack F. Greenblatt
Summary: Alternative polyadenylation (APA) enhances gene regulatory potential by increasing the diversity of mRNA transcripts. A study found that the transcription factor Sp1 binds RNA and is a common repressor of distal poly(A) site usage. Sp1 inhibits cleavage at distal sites by interacting with the subunits of the core cleavage and polyadenylation (CPA) machinery.
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
