Article
Chemistry, Multidisciplinary
Dong-Fang Zhao, Yu-Fan Fan, Fang-Yuan Wang, Fan-Bin Hou, Frank J. Gonzalez, Shi-Yang Li, Ping Wang, Yang-Liu Xia, Guang-Bo Ge, Ling Yang
Summary: The study identified Scutellariae radix as the most potent inhibitor of hCOMT among 53 herbal products. Specific chemicals like scutellarein, baicalein, and oroxylin A from the extract were found to be potent COMT inhibitors. These findings suggest the potential for developing more effective non-nitrocatechol COMT inhibitors for biomedical applications.
Article
Biochemistry & Molecular Biology
Wataru Kadowaki, Ryo Miyata, Misa Fujinami, Yoshizumi Sato, Shigenori Kumazawa
Summary: The study found that Calendula officinalis leaves contain 10 compounds with inhibitory activities against neurotransmitter-related diseases, particularly Parkinson's disease and depression.
Article
Biochemistry & Molecular Biology
Chuan-Ming Li, Le Chen, Guanjie Chen, Jianhua Zhang, Howard J. Hoffman
Summary: This study found a significant association between the COMT gene and hearing loss, with the A allele of rs6480 being linked to increased hearing loss. Among young adults in the United States, a missense variant of the COMT gene, rs4680, was significantly associated with hearing loss, shedding light on the genetic mechanisms of hearing loss.
Article
Chemistry, Medicinal
Dong-Fang Zhao, Yu-Fan Fan, Hao-Nan Yu, Fan-bin Hou, Yan-Wei Xiang, Ping Wang, Guang-Bo Ge, Ling Yang, Jian-Guang Xu
Summary: The study revealed that the flavonoids in vine tea exhibit strong inhibition against human catechol-Omethyltransferase, with myricetin being the most potent compound. This finding not only has implications for the drug exposure of catechol drugs, but also provides a promising lead compound for developing more effective hCOMT inhibitors.
Article
Agriculture, Multidisciplinary
Seul Hoo Lee, Bongsang Kim, Kyung-Jin Kim
Summary: The study reported the biochemical and structural analysis of COMT enzyme from Niastella koreensis, revealing that its activity is mainly influenced by magnesium ion, but also shows significant activity with copper and zinc ions. Structural analysis showed that the region near the SAM binding site undergoes conformational changes upon binding of the cosubstrate and the metal ion. Additionally, by developing variants, the activity and selectivity of NkCOMT can be enhanced.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Jin-Hee Kim, Jimin Lee, Hyesoo Jeong, Mi Seo Bang, Jin-Hyun Jeong, Minsun Chang
Summary: The study investigated the novel biological activities of NDGA in relation to COMT and how COMT inhibition by NDGA affects 4-OHE2-induced cyto- and genotoxicity in MCF-7 human breast cancer cells. The results showed that NDGA both inhibits COMT-mediated formation of 4-MeOE2 and increases 4-OHE2-induced DNA damage and cytotoxicity, potentially increasing catechol estrogen-induced genotoxicities in mammary tissues.
Article
Medicine, Research & Experimental
Andrea Polli, Jolien Hendrix, Kelly Ickmans, Jelena Bakusic, Manosij Ghosh, Dora Monteyne, Brigitte Velkeniers, Bram Bekaert, Jo Nijs, Lode Godderis
Summary: The study found associations between COMT haplotypes and DNA methylation, cytokine expression, and symptoms in patients with CFS/FM, but not specific to one condition. Significant differences were observed in increased DNA methylation in the MB-COMT promoter and decreased IFN-gamma expression in patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Medicinal
A. Katherine Hatstat, Grace M. Kennedy, Trevor R. Squires, Gisela Xhafkollari, C. Skyler Cochrane, Mauricio Cafiero, Larryn W. Peterson
Summary: L-DOPA, a dopamine precursor, is commonly used in Parkinson's disease treatment. Inhibiting COMT can prolong the effects of L-DOPA and dopamine, increasing the efficiency of the treatment. Nitrile derivatives with a nitro substituent show the most promise as COMT inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Health Care Sciences & Services
Hyemi Hwang, Yeonjae Han, Geun-Young Park, Soohwan Lee, Hae-Yeon Park, Sun Im
Summary: This study investigated the effects of tDCS on swallowing function in individuals with different COMT gene polymorphisms. The results showed that individuals with COMT Val/Val polymorphism experienced improvement in swallowing motor function after tDCS, while those with COMT Met carrier group did not show significant changes.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
K. Poonkuzhali, R. Seenivasagan, J. Prabhakaran, A. Karthika
Summary: Chemically engineered PLGA nanospheres inhibiting Catechol-O-methyltransferase (COMT) are a promising technology for treating neurodegenerative disorders. PLGA-MATPM nanospheres, synthesized using PLGA and MATPM, effectively inhibit COMT in a dose-dependent manner. The interaction between COMT and PLGA nanospheres is explained through spectroscopic and molecular dynamics analysis. PLGA-MATPM nanospheres show neurodegenerative recovery by suppressing the growth of neuroblastoma cells and effectively cross the blood-brain barrier.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Daniel Chavarria, Sofia Benfeito, Pedro Soares, Carla Lima, Jorge Garrido, Paula Serra, Patricio Soares-da-Silva, Fernando Remia, Paulo J. Oliveira, Fernanda Borges
Summary: CA derivatives have antioxidant properties and inhibitory effects on MAOs and COMT. They can protect cells against oxidative damage, but may induce ROS generation and cytotoxic effects at high concentrations. Some compounds can cross the blood-brain barrier, potentially aiding in restoring DA neurotransmission and preventing PD.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Fang-Yuan Wang, Ping Wang, Dong-Fang Zhao, Frank J. Gonzalez, Yu-Fan Fan, Yang-Liu Xia, Guang-Bo Ge, Ling Yang
Summary: This review summarizes recent advances in analytical methodologies for sensing COMT activity and their applications, while highlighting challenges and future perspectives in the field. The practical assays for measuring COMT activities in complex biological samples are crucial for investigating the relevance of COMT to human diseases and promoting the discovery of COMT inhibitors via high-throughput screening.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2021)
Article
Biochemistry & Molecular Biology
Ana M. Goncalves, Augusto Q. Pedro, Diana M. Oliveira, Adriana E. Oliveira, Marino F. A. Santos, Marcia A. S. Correia, Joao A. Queiroz, Eugenia Gallardo, Maria J. Romao, Luis A. Passarinha
Summary: This study characterized the thermal stability of SCOMT and found potential conditions and additives that can increase its stability and activity recovery rate. By using an ionic liquid and other additives, protein solubility and melting temperature were significantly improved, paving the way for further research and therapeutic molecule design.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ana M. Goncalves, Angela Sousa, Augusto Q. Pedro, Maria J. Romao, Joao A. Queiroz, Eugenia Gallardo, Luis A. Passarinha
Summary: Membrane-bound catechol-O-methyltransferase (MBCOMT) is a pharmacological target related to several types of human dementia, but its instability has hindered drug development. The addition of multi-component buffers and ionic liquids has shown promising results in enhancing the stability of MBCOMT and has important implications for drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Agriculture, Multidisciplinary
Ryo Miyata, Sara Hoshino, Mok-Ryeon Ahn, Shigenori Kumazawa
Summary: Bee pollen contains compounds that can competitively inhibit the neurotransmitter COMT, which is associated with Parkinson's disease and depression. This study analyzed the chemical composition of Korean bee pollens and identified key compounds with inhibitory properties. The findings suggest that bee pollen could be used for the prevention and treatment of these diseases.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Huaipan Jiang, Jian Wang, Weilin Cong, Yihe Huang, Morteza Ramezani, Anup Sarma, Nikolay Dokholyan, Mehrdad Mahdavi, Mahmut T. Kandemir
Summary: Modern drug discovery is costly and time-consuming. Computational approaches help reduce costs, but traditional software has low accuracy and high latency. MedusaGraph is a novel framework based on graph neural networks that generates docking poses directly and achieves 10 to 100 times speedup compared to current methods with slightly better accuracy.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Multidisciplinary
Weina Ke, Morgan Chandler, Edward Cedrone, Renata F. Saito, Maria Cristina Rangel, Mara de Souza Junqueira, Jian Wang, Da Shi, Nguyen Truong, Melina Richardson, Lewis A. Rolband, Didier Dreau, Peter Bedocs, Roger Chammas, Nikolay Dokholyan, Marina A. Dobrovolskaia, Kirill A. Afonin
Summary: This study introduces a biomolecular platform based on RNA-DNA anticoagulant fibers, which can communicate with thrombin and control coagulation through a kill-switch mechanism for restoring hemostasis. The research demonstrates the potential and advantages of this technology, showing good immunocompatibility and prolonged effectiveness.
Editorial Material
Pharmacology & Pharmacy
Kirill A. Afonin, Nikolay V. Dokholyan
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Mohammad Mahmoudi Gomari, Parastoo Tarighi, Edris Choupani, Shadi Abkhiz, Masoud Mohamadzadeh, Neda Rostami, Esmaeil Sadroddiny, Soukayna Baammi, Vladimir N. Uversky, Nikolay V. Dokholyan
Summary: One of the main obstacles in prevention and treatment of COVID-19 is the rapid evolution of the SARS-CoV-2 Spike protein, which can affect the effectiveness of treatments. The B.1.617.2 lineage of SARS-CoV-2, characterized by many Spike mutations, shows high infectivity and resistance to current treatments.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemical Research Methods
Damian Beasock, Anh Ha, Justin Halman, Martin Panigaj, Jian Wang, Nikolay V. Dokholyan, Kirill A. Afonin
Summary: The intrinsic properties of RNA and DNA biopolymers are highlighted by engineered nucleic acid nanoparticles (NANPs), which accelerate the development of next-generation therapies. The rational design of NANPs allows for programmable architectures to regulate molecular and cellular interactions. A novel concept of nuclease-driven production of NANPs is presented, where selective digestion of functionally inert structures leads to isothermal self-assembly of liberated constituents. The approach demonstrates the potential for regulating NANPs' stability, immunorecognition, and assembly to enhance the functionality of the system.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mikhail Liskovykh, Nikolai S. Petrov, Vladimir N. Noskov, Hiroshi Masumoto, William C. Earnshaw, David Schlessinger, Svetlana A. Shabalina, Vladimir Larionov, Natalay Kouprina
Summary: Although nucleoli are organelles without a limiting membrane, they have a unique structure built upon the rDNA-rich acrocentric short arms of five human chromosomes. Previous studies have suggested that sequences adjacent to the tandemly repeated rDNA units may be involved in the association of nucleolar organizer regions (NORs) with nucleoli. This study further investigated the requirements for NORs association with nucleoli, showing that transcription of constituent rDNA and the presence of heterochromatin blocks next to the rDNA arrays enhance this association. A small highly conserved DJ region and rDNA repeats are also implicated in the localization of acrocentric chromosome p-arms in nucleoli.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Multidisciplinary Sciences
Abha Jain, Nikolay V. Dokholyan, Andrew L. Lee
Summary: Optogenetics is a technique that uses light to directly control molecular function within living cells. This study focuses on the allosteric control of cell division control protein 42 (CDC42) by combining it with a light-sensing domain (LOV2). The research reveals the principles of action for this optoallosteric system and demonstrates that light or mutation-induced changes in LOV2 can inhibit CDC42 signaling. By monitoring the structural and dynamic properties using NMR spectroscopy, the study shows that the allosteric perturbations induced by light extend to the downstream effector binding sites of CDC42.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Brianna Hnath, Jiaxing Chen, Joshua Reynolds, Esther Choi, Jian Wang, Dongyan Zhang, Congzhou M. Sha, Nikolay V. Dokholyan
Summary: Protein aggregation leads to the formation of soluble oligomers and insoluble fibrils of different sizes. While fibrils were initially believed to cause neuronal cell death in neurodegenerative diseases, recent studies have demonstrated the toxicity of soluble oligomers. However, many therapeutic strategies still focus on fibrils or consider all aggregates as one group. Distinguishing between oligomers and fibrils and targeting the toxic species is crucial for successful study and therapeutic development.
Article
Pharmacology & Pharmacy
Balaji Chandrasekaran, Ashish Tyagi, Uttara Saran, Venkatesh Kolluru, Becca V. Baby, Venkat R. Chirasani, Nikolay V. Dokholyan, Jyh M. Lin, Amandeep Singh, Arun K. Sharma, Murali K. Ankem, Chendil Damodaran
Summary: We investigated the efficacy of ASR-600 in blocking androgen receptor (AR) and its splice variant AR-V7 signaling in castration-resistant prostate cancer (CRPC). ASR-600 effectively inhibited the growth of AR(+) CRPC cells by suppressing AR and AR-V7 expressions. It was found to bind to the N-terminal domain of AR, promote AR ubiquitination, and inhibit AR signaling. Stability studies showed that ASR-600 is stable and oral administration inhibits tumor growth in CRPC models.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Jiaxing Chen, Yashavantha L. Vishweshwaraiah, Richard B. Mailman, Erdem D. Tabdanov, Nikolay Dokholyan
Summary: Single-protein-based devices that integrate signal sensing with logical operations have the potential to monitor and modulate biological systems effectively. However, designing intelligent nanoscale computing agents with sensor domains integrated into functional proteins is challenging. In this study, the researchers incorporated a rapamycin-sensitive sensor and a blue light-responsive domain into a human Src kinase, creating a protein device that functions as a noncom-mutative combinatorial logic circuit. By applying the appropriate input signals, this protein device can reversibly control cell orientation, which has implications for tissue engineering and regenerative medicine.
Article
Immunology
Olga Matveeva, Svetlana A. Shabalina
Summary: The effect of vaccination/booster administration dynamics on excess mortality during COVID-19 infection waves in European countries was evaluated. The study found that faster vaccination countries performed better in protecting their residents from mortality throughout the pandemic. Slower booster rates were associated with higher mortality during periods dominated by the Omicron variant. Rating: 8/10.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Physical
Srinivas Niranj Chandrasekaran, Jhuma Das, Nikolay V. Dokholyan, Charles W. Carter
Summary: Mechanistic studies of Geobacillus stearothermophilus tryptophanyl-tRNA synthetase (TrpRS) provide a detailed description of the escapement mechanism, which efficiently converts the free energy of ATP hydrolysis into biologically useful alternative forms of information and work. Experimental and simulated melting of TrpRS reveal three transitions and ligands that stabilize the enzyme compress the temperature range over which these transitions occur. The TrpRS urzyme remains intact at the highest simulated temperatures.
STRUCTURAL DYNAMICS-US
(2023)
Article
Oncology
Negar Khazan, Emily R. R. Quarato, Niloy A. A. Singh, Cameron W. A. Snyder, Taylor Moore, John P. P. Miller, Masato Yasui, Yuki Teramoto, Takuro Goto, Sabeeha Reshi, Jennifer Hong, Naixin Zhang, Diya Pandey, Priyanka Srivastava, Alexandra Morell, Hiroki Kawano, Yuko Kawano, Thomas Conley, Deepak M. M. Sahasrabudhe, Naohiro Yano, Hiroshi Miyamoto, Omar Aljitawi, Jane Liesveld, Michael W. W. Becker, Laura M. M. Calvi, Alexander S. S. Zhovmer, Erdem D. D. Tabdanov, Nikolay V. V. Dokholyan, David C. C. Linehan, Jeanne N. N. Hansen, Scott A. A. Gerber, Ashoke Sharon, Manoj K. K. Khera, Peter W. W. Jurutka, Natacha Rochel, Kyu Kwang Kim, Rachael B. B. Rowswell-Turner, Rakesh K. K. Singh, Richard G. G. Moore
Summary: The study identifies vitamin D/VDR as the driver of PD-L1 expression in AML and other cancers. They have developed a small molecule inhibitor called MeTC7 to target PD-L1 and inhibit tumorigenesis driven by PD-L1/PD-1. This provides a potential alternative to antibodies for controlling immune evasion in tumors.
Meeting Abstract
Oncology
Ashish Tyagi, Balaji Chandrasekaran, Uttara Saran, Murali K. Ankem, Nikolay Dokholyan, Jyh M. Lin, Arun K. Sharma, Chendil Damodaran
Article
Clinical Neurology
Nikolay Dokholyan, Richard C. Mohs, Randall J. Bateman
Summary: The health, well-being, and financial security of Americans are significantly affected by Alzheimer's disease. The number of Americans suffering from Alzheimer's disease and related dementia is expected to increase. A hearing titled "The Alzheimer's Crisis: Examining, Testing, and Treatment Pipelines and Fiscal Implications" was held by The Senate Committee on Finance, Subcommittee on Health Care on December 16, 2020 to discuss the crisis. The panel reviewed recent progress, ongoing challenges, and potential initiatives to accelerate treatment development and improve care.
ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS
(2022)