Article
Biochemistry & Molecular Biology
Qian Jia, Hui Zeng, Mingwei Li, Jing Tang, Nan Xiao, Shangfang Gao, Huanxi Li, Jinbing Zhang, Zhiyong Zhang, Wei Xie
Summary: This study investigates the structure and function of guanosine deaminase (GSDA). By analyzing the cocrystal structures of Arabidopsis thaliana GSDA bound by inactive guanosine derivatives, it is found that the binding performances of the two protomers are unequal, and molecular dynamics simulation confirms diverse conformations during the enzyme-ligand interactions. Furthermore, tripartite salt bridges between subunits are identified to play a role as gating systems for substrate binding and product release.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Fabio Jose Bonfim Cardoso, Luciana Pereira Xavier, Agenor Valadares Santos, Humberto D'Muniz Pereira, Lourivaldo da Silva Santos, Fabio Alberto de Molfetta
Summary: Neolignans show potential inhibition of the enzyme activity of Schistosoma mansoni, with molecular docking and dynamics studies indicating stable inhibition. Biological assays suggest neolignans as promising candidates for future chemotherapy research on schistosomiasis.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Asmita Sen, Vandana Gaded, Prabha Jayapal, Gopalan Rajaraman, Ruchi Anand
Summary: Guanine deaminases (GD) are essential enzymes for regulating the nucleobase pool. The study on GD from Nitrosomonas europaea reveals the mechanism of substrate fidelity, involving two amino acids (E79 and E143) and the presence of crystallographic water molecules near the active site that control reactivity. The proposed catalytic mechanism can be applied to design selective inhibitors for human GD.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Biochemistry & Molecular Biology
Qian Jia, Jinbing Zhang, Hui Zeng, Jing Tang, Nan Xiao, Shangfang Gao, Huanxi Li, Wei Xie
Summary: The inactivity of AtGSDA is attributed to its inability to seclude the active site and the lack of functional amino groups or poor interactions/geometries of the ligands at the active sites.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Qian Jia, Hui Zeng, Huanxi Li, Nan Xiao, Jing Tang, Shangfang Gao, Jinbing Zhang, Wei Xie
Summary: In this study, the researchers determined the structures of GSDA in plants, revealing its catalytic mechanism and structural rearrangements during reactions. The identification of additional substrates and comparison with other deaminases helped uncover recognition differences for specific substrates. These findings may contribute to the development of deaminase-based gene-editing tools.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Amit Kumar, Harish Vashisth
Summary: Riboswitches are conserved functional domains in bacteria that specifically bind small molecules to regulate biosynthesis and transport of amino acids and essential metabolites. They have potential as antibacterial drug targets and this study investigated the recognition mechanisms of oxidized metabolites by the NMT1 riboswitch. Electrostatic interactions were found to be central to ligand discrimination and some mutations could strengthen the binding affinities of the ligands. These findings are also relevant for designing novel compounds targeting riboswitches.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Yongxin Zheng, Yinping Huang, Jun Mencius, Yanjing Li, Lijie Zhao, Wanting Luo, Yong Chen, Shu Quan
Summary: MLL3 and MLL4 utilize distinct kinetic mechanisms in catalyzing the monomethylation of histone H3 lysine 4, which may provide insights into their differential functions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Rosa Maria Vitale, Fabio Arturo Iannotti, Aniello Schiano Moriello, Lea Tunisi, Fabiana Piscitelli, Ranjev Savopoulos, Luigia Cristino, Luciano De Petrocellis, Pietro Amodeo, Roy Gray, Vincenzo Di Marzo
Summary: The study provides the first evidence that CBD acts as an antagonist at the OX1R receptor, supporting its potential use in addictive disorders and/or body weight regulation.
Article
Biochemistry & Molecular Biology
Rashmi Tyagi, Mitul Srivastava, Preeti Jain, Ramendra Pati Pandey, Shailendra Asthana, Dhruv Kumar, V. Samuel Raj
Summary: Tuberculosis is declared a health emergency due to the increasing problem of Multidrug-resistant Tuberculosis (MDR-TB) worldwide. This study identifies potential therapeutic approach against MDR-TB by screening small molecule compounds and validating their efficacy in inhibiting Mycobacterium tuberculosis growth. Molecular docking and simulation analysis show strong and stable interaction between the lead compounds and Mycobacterium tuberculosis proteasome, with no cytotoxicity effect on human proteasome.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Elham Sadat Mostafavi, Ahmad Asoodeh, Jamshidkhan Chamani
Summary: This study analyzed the interaction between Ponceau 4R (P4R) and trypsin using spectroscopic, kinetic, and theoretical methods. The results revealed that P4R can bind to trypsin, inhibit its activity, and alter its conformation, which can affect its function.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Environmental Sciences
Lili Wang, Anjie Li
Summary: This study investigates the molecular mechanism of EE2 degradation by AOB and AMO using a combination of experimental and computational simulation methods. The results reveal that ammonia nitrogen is essential for the co-metabolism of EE2 by AOB, and NH3 binds with CuC to induce a conformational change in AMO, enabling EE2 to bind with CuB and undergo biological transformation. These findings provide a theoretical basis and a novel research perspective on the removal of ammonia nitrogen and emerging contaminants in wastewater treatment.
ENVIRONMENTAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Norburhanuddin Johari Zaidi, Adib Afandi Abdullah, Choon Han Heh, Chun-Hung Lin, Rozana Othman, Abdullah Al Hadi Ahmad Fuaad
Summary: The global incidence of dengue infection is rising, but no therapeutic treatment is available. This study used computational methods to identify potential dengue virus inhibitory peptides, and the in vitro results validated the computational findings, highlighting the value of computational research in the lead optimization of antiviral peptides.
Article
Biochemistry & Molecular Biology
Irengbam Rocky Mangangcha, Raj Kumar Brojen Singh, Djamel Lebeche, Shakir Ali
Summary: The study identifies a natural xanthonoid, beta DGT, as a potential ATP-competitive inhibitor of GSK3 beta that could be beneficial in reducing cardiovascular disease risk in prostate cancer patients undergoing ADT.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Mashooq A. A. Bhat, Burak Tuzun, Nawaf A. A. Alsaif, Azmat Ali M. Khan, Ahmed M. Naglah
Summary: A novel series of purine derivatives containing sulfonamide moiety were successfully synthesized using a single-step reaction method. The purity and structure of the compounds were confirmed by various characterization and analysis techniques. Computational studies and experimental comparisons revealed that one of the compounds exhibited high activity in the interaction with EGFR proteins. Additionally, drug properties of the molecules were investigated.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Agricultural Engineering
Francisco Thalysson Tavares Cavalcante, Aluisio Marques da Fonseca, Jeferson Yves Nunes Holanda Alexandre, Jose C. S. dos Santos
Summary: Biolubricants derived from renewable raw materials and synthesized using enzymes have gained market attention. This study focuses on the synthesis reactions of biolubricants using the genetically-modified lipase Eversa (R) Transform 2.0. Computational tools, such as docking and molecular dynamics, were employed to understand the interactions and stability of enzyme-ligand complexes. In vitro validation confirmed the improved esterification activity of the lipase with isoamyl alcohol, suggesting its potential in the biolubricant production system.
INDUSTRIAL CROPS AND PRODUCTS
(2022)
Article
Neurosciences
Anton Omelchenko, Harita Menon, Sarah G. Donofrio, Gaurav Kumar, Heidi M. Chapman, Joshua Roshal, Eduardo R. Martinez-Montes, Tiffany L. Wang, Mark R. Spaller, Bonnie L. Firestein
MOLECULAR NEUROBIOLOGY
(2020)
Article
Cell & Tissue Engineering
Nisha K. Singh, Salman Khaliq, Mann Patel, N'Dea Wheeler, Sudeepti Vedula, Joseph W. Freeman, Bonnie L. Firestein
Summary: Spinal cord injury (SCI) is characterized by primary mechanical injury and secondary pathological damage, with glutamate-induced excitotoxicity (GIE) being a major event in secondary SCI. Uric acid (UA) shows promise as a therapeutic candidate to protect neurons from GIE damage. Using fiber mats for local UA release is a promising therapeutic approach to reduce secondary damage in patients with SCI.
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
(2021)
Article
Cell & Tissue Engineering
Richard N. Cliver, Brian Ayers, Alyssa Brady, Bonnie L. Firestein, Maribel Vazquez
Summary: Disorders of the nervous system impact millions of adults globally, and studies have shown the potential benefits of incorporating neuroglia into emerging therapies, as well as the partially explored role of cerebrospinal fluid in such treatments. Tested in vitro, EBS solutions demonstrate positive effects on glial cells and neurite extension, highlighting the translational significance of using CSF replacement fluids in regenerative NS therapies.
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
(2021)
Article
Neurosciences
Yasmin H. Ramadan, Amanda Gu, Nicole Ross, Sara A. McEwan, Maureen M. Barr, Bonnie L. Firestein, Robert O'Hagan
Summary: Microtubules are essential for neuronal survival and communication in the nervous system. The enzyme CCP1 has been found to protect spinal cord neurons from excitotoxic death, independent of cilia. Targeting MT polyglutamylation regulators like CCP1 could potentially prevent excitotoxic death after spinal cord injuries.
Article
Mathematical & Computational Biology
Rosalind E. Mott, Catherine R. von Reyn, Bonnie L. Firestein, David F. Meaney
Summary: Traumatic brain injury is a devastating public health issue globally, with studies showing that mechanically injured neurons inactivate and eventually re-integrate into neural networks depending on their activity level and initial connections. Modulating neuronal activity post-injury can help rescue neurons, with inhibition of activity more effective than activation. Mitochondrial energetics also play a role in rescuing neurons after mechanical trauma.
FRONTIERS IN COMPUTATIONAL NEUROSCIENCE
(2021)
Review
Cell Biology
Chelsea Schiliro, Bonnie L. Firestein
Summary: Cancer cells alter metabolic processes to sustain their rapid growth, including shifting from oxidative phosphorylation to aerobic glycolysis, and increasing other pathways to generate necessary molecules.
Article
Biotechnology & Applied Microbiology
Emily Kolaya, Bonnie L. Firestein
Summary: Deep brain stimulation (DBS) is used for treating motor symptoms of Parkinson's disease by stimulating the subthalamic nucleus, but there is still a need for optimization due to limitations of neural electrodes caused by the body's response. Current solutions to technical issues include modifications to electrode material, coatings, and geometry.
BIOTECHNOLOGY PROGRESS
(2021)
Article
Neurosciences
Chen Liang, Damien Carrel, Nisha K. Singh, Liam L. Hiester, Isabelle Fanget, Hyuck Kim, Bonnie L. Firestein
Summary: Neuronal migration and dendritogenesis are dependent on dynamic changes to the microtubule network. Post-translational modifications (PTMs) of microtubules, particularly tubulin polyglutamylation, play a critical role in regulating these processes. The carboxypeptidase E (CPE) protein has been identified as a regulator of tubulin polyglutamylation, and this study investigates the impact of CPE-mediated changes on cortical neuron migration and dendrite morphology. The results show that CPE can modulate polyglutamylation levels and affect the localization of p150 (Glued), suggesting a role for CPE in regulating microtubule dynamics and cortical neuron migration. The function of CPE in dendrite development appears to be independent of its role in polyglutamylation, as a CPE mutant that does not affect glutamylation still affects dendrite branching.
Article
Engineering, Biomedical
Siddhant Kumarapuram, Ansley J. Kunnath, Anton Omelchenko, Nada N. Boustany, Bonnie L. Firestein
Summary: The stiffness of substrates affects mitochondrial characteristics and dendritic morphology of neurons, with glutamate receptors playing a crucial role in mediating these effects. Neurons grown on softer substrates have smaller and simpler dendritic mitochondria, while neurons grown on stiffer substrates exhibit larger, more complex dendritic mitochondria. The manipulation of NMDA and AMPA receptors on neurons grown on stiffer substrates leads to mitochondrial characteristics resembling those of neurons grown on softer substrates, indicating the important regulatory roles of glutamate receptors in response to substrate stiffness.
ANNALS OF BIOMEDICAL ENGINEERING
(2022)
Article
Neurosciences
Eric S. Sweet, Keith R. Lange, Madeleine R. Fenner, Chia-Yi Tseng, Barbara F. Akum, Bonnie L. Firestein
Summary: Cypin is a multifunctional protein that plays a major role in shaping the morphology of dendritic arbor of neurons. It catalyzes the deamination of guanine, leading to the polymerization of microtubules. Cypin binds to microtubule heterodimers and facilitates their polymerization. Overexpression of Cypin results in decreased spacing between microtubules.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2022)
Correction
Cell Biology
Chelsea Schiliro, Bonnie L. Firestein
Editorial Material
Neurosciences
Bonnie L. Firestein
MOLECULAR AND CELLULAR NEUROSCIENCE
(2023)
Article
Pharmacology & Pharmacy
Kiran Deshpande, Keith R. R. Lange, William B. B. Stone, Christine Yohn, Naomi Schlesinger, Leonid Kagan, Albert J. J. Auguste, Bonnie L. L. Firestein, Luigi Brunetti
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces systemic inflammation, resulting in organ damage. This study identifies changes in the expression of drug transporters and metabolizing enzymes in the liver, kidneys, and lungs of infected mice. These findings highlight the importance of considering altered drug disposition and processing in the development of therapeutic compounds.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2023)
Article
Neurosciences
Ana R. Rodriguez, Erin D. Anderson, Kate M. O'Neill, Przemyslaw P. McEwan, Nicholas F. Vigilante, Munjin Kwon, Barbara F. Akum, Tamara M. Stawicki, David F. Meaney, Bonnie L. Firestein
Summary: The study demonstrates that cypin affects synaptic function by regulating PSD-95 content, reducing PSD-95 clusters and increasing mEPSC frequency. Overexpression of cypin increases AMPA receptor function independently of PSD-95 localization, indicating a critical role of cypin in neural circuit changes. This research reveals that cypin promotes alterations in AMPA receptor signaling, shaping neural circuits and influencing information relay among brain regions beyond the hippocampus.
NETWORK NEUROSCIENCE
(2021)
Review
Engineering, Biomedical
Anton Omelchenko, Nisha K. Singh, Bonnie L. Firestein
CURRENT OPINION IN BIOMEDICAL ENGINEERING
(2020)