Article
Biochemistry & Molecular Biology
Kai Halwas, Lennard-Maximilian Doering, Franziska Valentina Oehlert, R. Juergen Dohmen
Summary: Polyamines are important biogenic polycations that play essential roles in various cellular processes and diseases. The biosynthesis of polyamines involves the conversion of ornithine to putrescine by ornithine decarboxylase (ODC). The regulation of ODC by ODC antizyme (OAZ) involves a unique mechanism of posttranslational regulation through polyamine-regulated bypassing of an internal translation termination codon. The depletion of polyamines inhibits translation across the OAZ1 ribosomal frameshift (RFS) site by affecting eIF5A hypusination and RFS directly.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Danish Idrees, Ahmad Abu Turab Naqvi, Md Imtaiyaz Hassan, Faizan Ahmad, Samudrala Gourinath
Summary: This study investigates the effect of urea on the structure and stability of SAT1 and SAT3 enzymes in Entamoeba histolytica. The results show that SAT1 is more stable than SAT3, and urea causes a transition from α-helix to β-sheet conformation and burial of tryptophan residues. Molecular dynamics simulations support these findings.
Article
Biochemistry & Molecular Biology
Tolbert Osire, Zhina Qiao, Taowei Yang, Meijuan Xu, Xian Zhang, Zhiming Rao
Summary: Inducible lysine decarboxylases (LDCs) play essential roles in various cellular processes in microorganisms and plants, especially under acid stress. A novel Serratia marcesenes LDC (SmcadA) was successfully expressed, purified, and characterized, with the highest specific activity found in the Arg595Lys mutant. Molecular dynamics simulations highlighted the importance of hydrogen bonds between protein residues and cofactor PLP in biocatalysis. These findings contribute to understanding protein-cofactor interactions and improving biocatalysis efficiency.
Article
Biochemistry & Molecular Biology
Li Zong, Guorong Cheng, Jingwu Zhao, Xiaoyu Zhuang, Zhong Zheng, Zhiqiang Liu, Fengrui Song
Summary: The natural compound Ursolic acid (UA) has been found to inhibit the invasion and metastasis of drug-resistant breast cancer cells (MCF-7/ADR) by targeting the ornithine decarboxylase (ODC) pathway, as well as regulating the MAPK-Erk-VEGF/MMP-9 signaling pathways and polyamine metabolism. This study suggests that UA may have potential therapeutic effects in breast cancer treatment.
Article
Chemistry, Multidisciplinary
Joanna Bojarska, Roger New, Pawel Borowiecki, Milan Remko, Martin Breza, Izabela D. Madura, Andrzej Fruzinski, Anna Pietrzak, Wojciech M. Wolf
Summary: The article presents a comprehensive study on the molecular and supramolecular structure of DFMO, aiming to design safer and more effective drug formulations. By delving into the interactions of DFMO, the study explores its different cooperative mechanisms in supramolecular self-assembly compared to the ornithine structure. Additionally, the importance of amino acids in drug discovery is discussed in the context of the research.
FRONTIERS IN CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Helios Cardenas-Hernandez, Gustavo A. Titaux-Delgado, Elizabeth J. Castaneda-Ortiz, Alfredo Torres-Larios, Luis G. Brieba, Federico del Rio-Portilla, Elisa Azuara-Liceaga
Summary: The research focused on analyzing the genome and structure of a specific transcription factor in Entamoeba histolytica, showing differences between Myb-SHAQKYF proteins and proteins from other families. The study suggests a potential role for these proteins in the life cycle of E. histolytica.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2021)
Article
Chemistry, Medicinal
Sandeep Lohan, Dindyal Mandal, Wonsuk Choi, Anastasia G. Konshina, Rakesh K. Tiwari, Roman G. Efremov, Innokentiy Maslennikov, Keykavous Parang
Summary: The study reports the synthesis of amphiphilic membrane-active peptides with broad-spectrum antibacterial activity, particularly effective against drug-resistant bacteria. The cyclic peptides were found to be more stable compared to their linear counterparts, and capable of disrupting bacterial cell membranes. Nuclear magnetic resonance spectroscopy and molecular dynamics simulation revealed the interaction mechanisms between these peptides and cell membranes.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Nischal Karki, Satyam Vergish, Brian D. Zoltowski
Summary: The review examines the differences in photochemistry and signal transduction in plant and animal CRYs, identifying potential modes of convergent evolution within these lineages that may reveal conserved signaling pathways. Recent data provides clarity on potential mechanisms of signal transduction in magnetoreception, addressing the conflicts regarding CRY photochemistry and signal transduction.
Article
Multidisciplinary Sciences
Joseph S. Snowden, Jehad Alzahrani, Lee Sherry, Martin Stacey, David J. Rowlands, Neil A. Ranson, Nicola J. Stonehouse
Summary: This study reanalyzed the structure of type I fatty acid synthases (FASs) and identified several differences in both structural and enzymatic domains between P. pastoris FAS and the prototypical yeast FAS from S. cerevisiae. By using focussed classification, the researchers were able to resolve and model the mobile acyl-carrier protein (ACP) domain, which is crucial for the function of FAS. The structure reported in this study will serve as a valuable resource for further engineering efforts to synthesize alternate products using yeast FAS.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Yidong Wang, Lixia Wang, Zeyuan Guan, Hongfei Chang, Ling Ma, Cuicui Shen, Liang Qiu, Junjie Yan, Delin Zhang, Jian Li, Xing Wang Deng, Ping Yin
Summary: The COP1-SPA complex acts as a central repressor of photomorphogenesis, and the activity of COP1-SPA is repressed by UV-B-activated UVR8 through competitive binding, which is derepressed by RUP2.
Article
Biochemistry & Molecular Biology
Linchang Dai, Yaxin Dai, Jinhua Han, Yan Huang, Longge Wang, Jun Huang, Zheng Zhou
Summary: The study reveals the mechanism of BRCA1-BARD1 complex recruitment and retention by DSB-flanking nucleosomes, shedding light on cancer therapeutic avenues.
Article
Biochemistry & Molecular Biology
Jianjun Cao, Matthew J. Belousoff, Elliot Gerrard, Radostin Danev, Madeleine M. Fletcher, Emma Dal Maso, Herman Schreuder, Katrin Lorenz, Andreas Evers, Garima Tiwari, Melissa Besenius, Ziyu Li, Rachel M. Johnson, Denise Wootten, Patrick M. Sexton
Summary: Amylin receptors (AMYRs) are promising obesity targets, and modification to residues 19-22 can result in selective activation of AMYRs. The study found that San45, with its conjugated lipid at position 21, can bind to the calcitonin receptor (CTR) in a stable, alternative binding mode, providing a potential intervention strategy for the design of long-acting, nonselective, Amy-based anti-obesity drugs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nishant Singh, Sarah Naiyer, Sudha Bhattacharya
Summary: Entamoeba histolytica is a pathogenic parasite responsible for amoebiasis, using the human colon to complete its life cycle. A study using electron microscopy on a reptilian parasite, Entamoeba invadens, revealed ultrastructural changes during encystation, showing an increase in heterochromatin patches and deformation of nuclear shape as early events. This study opens up possibilities for further investigation into the mechanisms involved in this novel process.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Lian Wu, Zhanfeng Wang, Yixin Cen, Binju Wang, Jiahai Zhou
Summary: This study provides the complex structure of FtmOx1, revealing the interaction between fumitremorginB and the substrate. The results support a CarC-like catalytic mechanism and emphasize the importance of accurate complex structures in the mechanistic study of enzymatic catalysis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Shuyan Dai, Lingzhi Qu, Jun Li, Ye Zhang, Longying Jiang, Hudie Wei, Ming Guo, Xiaojuan Chen, Yongheng Chen
Summary: The aryl hydrocarbon receptor (AHR), an important transcription factor, plays significant roles in regulating xenobiotic metabolism, cellular differentiation, and immunity. This study provides multiple crystal structures of the Drosophila AHR PAS-B domain, which sheds light on the mechanism of AHR ligand binding. These findings have implications for the development of AHR-targeted therapeutics.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Neema Kumari, Vikram Dalal, Pravindra Kumar, Subha Narayan Rath
Summary: Studies have shown that blocking the T-type calcium channel (TTCC) in cancer cells can overcome drug resistance. This study used computational analysis to test the binding of TTA-A2 and PTX with TTCC, and confirmed the in-silico result with in vitro experiments using a 3D spheroid model. The results indicate that sequential treatment can help overcome the antagonistic interaction between these two drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Microbiology
Aakriti Dubey, Shweta Choudhary, Pravindra Kumar, Shailly Tomar
Summary: The sudden rise in COVID-19 cases in 2020 and the emergence of fast-spreading variants have created a worrisome situation worldwide. New variants with mutations that outcompete existing circulating variants are frequently reported, raising concerns about the efficacy of vaccines, increased transmissibility, immune escape, and diagnostic failures. Although not yet validated, it is believed that SARS-CoV-2 is acquiring new mutations to gain a fitness advantage for rapid transmission or to overcome immune resistance. Significant evolution of SARS-CoV-2 has been observed since its first appearance in 2019, but the impacts of these mutations in many variants have not been analyzed. This article provides a comprehensive review of the emerging variants of SARS-CoV-2, key mutations in the viral genome, and the possible impacts on current prevention and therapeutic strategies.
CURRENT MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Akshay Pareek, Ravi Kumar, Rajat Mudgal, Neetu Neetu, Monica Sharma, Pravindra Kumar, Shailly Tomar
Summary: Alphaviruses pose a global threat to human health and there is currently no commercially available antiviral drug for alphaviral infections. This study identifies and validates the antiviral efficacy of small molecules targeting the RNA-dependent RNA polymerase (RdRp) of alphavirus non-structural protein nsP4. Four potential inhibitors were identified and shown to have antiviral potency against CHIKV. The findings pave the way for the development of broad-spectrum alphavirus antivirals targeting nsP4 RdRp.
Article
Microbiology
Jai Krishna Mahto, Neetu Neetu, Monica Sharma, Monika Dubey, Bhanu Prakash Vellanki, Pravindra Kumar
Summary: This study investigated the structure and catalytic characteristics of TPDO from Comamonas testosteroni KF1 (TPDOKF1), revealing its interaction with TPA and the catalytic mechanism. The findings of this study have important implications for addressing global plastic pollution.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Md Shahid Alam, Monica Sharma, Rakesh Kumar, Joy Das, Surabhi Rode, Pravindra Kumar, Ramasare Prasad, Ashwani Kumar Sharma
Summary: The study aimed to identify effective small inhibitory molecules for controlling the Helicoverpa armigera pest. Virtual screening and docking studies identified three molecules with good binding affinities, and molecular dynamics simulation analysis confirmed the formation of stable complexes. These findings provide potential candidates for developing environmentally friendly insect growth regulators.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Vikram Dalal, Dasantila Golemi-Kotra, Pravindra Kumar
Summary: This study identified a novel esterase called FmtA, which hydrolyzes D-Ala in teichoic acids. Molecular simulations revealed that specific residues in the active site play a crucial role in substrate binding, and the catalysis involves a series of complex reaction steps.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Madhusudhanarao Katiki, Neetu Neetu, Shivendra Pratap, Pravindra Kumar
Summary: This study reports the crystal structures of FabI from Moraxella catarrhalis in different complex forms, showing that TCL and EST inhibit the activity of McFabI and affect cell growth.
Article
Biotechnology & Applied Microbiology
Madhusudhanarao Katiki, Monica Sharma, Neetu Neetu, Madhubala Rentala, Pravindra Kumar
Summary: This study aims to identify inhibitors against DOHH from Leishmania donovani for the treatment of Leishmaniasis. The LdDOHH protein was produced and characterized. Virtual screening identified folic acid, scutellarin, and homoarbutin as potential inhibitors, which were found to bind in the active site of LdDOHH and stabilize the structure.
BRIEFINGS IN FUNCTIONAL GENOMICS
(2023)
Article
Biochemistry & Molecular Biology
Rakesh Kumar, Joy Das, Jai Krishna Mahto, Monica Sharma, Shah Vivek, Pravindra Kumar, Ashwani Kumar Sharma
Summary: This study investigates the structural and functional characterization of farnesol dehydrogenase in Helicoverpa armigera, a major cotton pest. The results show that the enzyme exists as a soluble homo-tetrameric form, exhibits broad substrate affinity, and is involved in the synthesis of juvenile hormone in insects. The crystal structure and substrate modeling provide insights into the enzyme's mechanism and substrate binding properties.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Namrata Chakravarty, Monica Sharma, Pravindra Kumar, R. P. Singh
Summary: This study presents an improved version of L-asparaginase called BaAsp, which lacks glutaminase activity. BaAsp exhibits substrate selectivity and specificity, and shows maximum enzyme activity under specific conditions. In silico analysis also reveals a conserved zinc-binding site in BaAsp. These findings provide valuable insights for the development of alternative antileukemic drugs.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Deena Nath Gupta, Vikram Dalal, Brajesh Kumar Savita, Md Shahid Alam, Anamika Singh, Mrugendra Gubyad, Dilip Kumar Ghosh, Pravindra Kumar, Ashwani Kumar Sharma
Summary: In this study, the Bacterioferritin comigratory protein family 1 Cys peroxiredoxin from Candidatus Liberibacter asiaticus (CLaBCP) was biochemically studied and screened for potential antibacterial molecules. The results showed that CLaBCP has enzymatic activity and undergoes structural changes at different pH and temperature ranges. A structure-based drug design method was used to identify more efficient molecules, and molecular dynamics studies confirmed their stability.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Jai Krishna Mahto, Monica Sharma, Neetu Neetu, Arpan Kayastha, Shubham Aggarwal, Pravindra Kumar
Summary: In this study, the second enzyme of the phthalate catabolic pathway, PhtC(KF1), was characterized and found to have catalytic efficiency over 10 fold higher with cis-4,5-dihydrodiol phthalate (DDP) than with cis-3,4-dihydrodiol phthalate (CDP). Crystal structures of PhtC(KF1) in different complexes revealed that the binding of 3-hydroxybenzoate (3HB) induces a conformational change in the substrate-binding loop and the catalytic domain of PhtC(KF1) is larger than other homologs. Mutational analysis further confirmed the importance of conformational flexibility of the substrate-binding loop for the dehydrogenation activity. The study also proposed a reaction mechanism and explained the broader substrate specificity of this enzyme based on crystal structures and biochemical analysis.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Biochemical Research Methods
Vishakha Singh, Poonam Dhankhar, Vikram Dalal, Shailly Tomar, Pravindra Kumar
Summary: This study aimed to investigate the drug target for Klebsiella pneumonia and identify potential antibacterial compounds. Through in-silico analysis and bioinformatics tools, HP CP995_08280 was identified as a drug target and five potent antibacterial molecules were discovered. Molecular dynamics and MMPBSA confirmed the stability of the complexes.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2022)
Article
Chemistry, Multidisciplinary
Vishakha Singh, Poonam Dhankhar, Vikram Dalal, Shailly Tomar, Dasantila Golemi-Kotra, Pravindra Kumar
Summary: In this study, virtual screening and molecular dynamics simulations were carried out to identify potential drug molecules targeting FmtA, a key factor associated with methicillin resistance in Staphylococcus aureus. The top-ranked compounds, gemifloxacin, paromomycin, streptomycin, and tobramycin, showed high binding affinity and formed stable protein-inhibitor complexes. Experimental binding studies confirmed the strong binding affinity between these molecules and FmtA, providing potential starting points for the development of advanced antibacterial agents.
Article
Biochemistry & Molecular Biology
Poonam Dhankhar, Vikram Dalal, Ashwani Kumar Sharma, Pravindra Kumar
Summary: Dye-decolorizing peroxidases (DyPs) are enzymes that catalyze the oxidation of industrial dyes, lignin, and lignin model compounds. Previous studies have shown the crystal structures of DyPs at acidic pH, revealing the optimal conditions for enzyme activity.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)