Phosphotransfer and Nucleotidyltransfer

2007 ◽  
Author(s):  
Perry A. Frey ◽  
Adrian D. Hegeman
Keyword(s):  
Transition State ◽  
Molecular Mechanisms ◽  
Enzymatic Reaction ◽  
Covalent Bond ◽  
Phosphoryl Group ◽  
Dissociative Mechanism ◽  
Chemical Mechanisms ◽  
Cellular Processes ◽  
Nucleic Acid Biosynthesis ◽  
Transfer Mechanisms

Phosphotransferases, phosphatases, and nucleotidyltransferases catalyze nucleophilic substitution at phosphorus. They constitute a dominant class of enzymes in intermediary metabolism, energy transduction, nucleic acid biosynthesis and processing, and regulation of many cellular processes, including replication, cellular development, and apoptosis. The mechanisms of the action of these enzymes have been studied intensively at several levels, ranging from the biosynthesis of metabolites and nucleic acids to unmasking signaling networks to elucidating the molecular mechanisms of catalysis. We focus on the chemical mechanisms of the reactions of biological phosphates. More than 40 years of research on this chemistry reveals that the mechanisms can be grouped into two classes: the phosphoryl group (PO3−) transfer mechanisms and the nucleotidyl or alkylphosphoryl group (ROPO2−) transfer mechanisms. Because the fundamental chemical mechanisms of these reactions are not treated in textbooks, we begin by considering this chemistry and then move on to the enzymatic reaction mechanisms. Phosphomonoesters, phosphoanhydrides, and phosphoramidates undergo substitution at phosphorus by transfer of the phosphoryl (PO3–) group, that is, by P—O and P—N cleavage. The current description of a typical phosphoryl group transfer mechanism is one in which the phosphoryl donor and acceptor interact weakly with the phosphoryl group in flight in a transition state in which the total bonding to phosphorus is decreased relative to the ground state. The bonding is weak between phosphorus and the leaving group R–X and between phosphorus and the accepting group Y in the transition state of. Because of decreased bonding to phosphorus, this is a loose transition state that has been described as dissociative. The latter should not be confused with the dissociative mechanism, which is considered later. To avoid confusion, we use the term loose transition state. Detailed studies indicate that the bonding denoted by the dashed lines in represents partial covalency on the order of 10% to 20% of the strength of a full covalent bond, or a bond order of 0.1 to 0.2.

scholarly journals Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

2021 ◽  
Vol 11 (6) ◽  
pp. 513
Author(s):  
Zheng Zhang ◽  
Meng Gu ◽  
Zhongze Gu ◽  
Yan-Ru Lou
Keyword(s):  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Cellular Processes ◽  
Dna And Rna ◽  
Chemotherapeutic Response ◽  
Non Coding Rna ◽  
Response To Chemotherapy ◽  
Personalized Oncology ◽  
Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

scholarly journals DEAD-box helicases modulate dicing body formation in Arabidopsis

2021 ◽  
Vol 7 (18) ◽  
pp. eabc6266
Author(s):  
Qi Li ◽  
Ningkun Liu ◽  
Qing Liu ◽  
Xingguo Zheng ◽  
Lu Lu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Turnip Mosaic Virus ◽  
Liquid Droplets ◽  
Phase Separations ◽  
Body Formation ◽  
Cellular Processes ◽  
Dead Box ◽  
Body Components ◽  
Liquid Phase Separations ◽  
Spatiotemporal Control

Eukaryotic cells contain numerous membraneless organelles that are made from liquid droplets of proteins and nucleic acids and that provide spatiotemporal control of various cellular processes. However, the molecular mechanisms underlying the formation and rapid stress-induced alterations of these organelles are relatively uncharacterized. Here, we investigated the roles of DEAD-box helicases in the formation and alteration of membraneless nuclear dicing bodies (D-bodies) in Arabidopsis thaliana. We uncovered that RNA helicase 6 (RH6), RH8, and RH12 are previously unidentified D-body components. These helicases interact with and promote the phase separation of SERRATE, a key component of D-bodies, and drive the formation of D-bodies through liquid-liquid phase separations (LLPSs). The accumulation of these helicases in the nuclei decreases upon Turnip mosaic virus infections, which couples with the decrease of D-bodies. Our results thus reveal the key roles of RH6, RH8, and RH12 in modulating D-body formation via LLPSs.

scholarly journals A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1

2021 ◽  
Vol 22 (14) ◽  
pp. 7390
Author(s):  
Nicole Wesch ◽  
Frank Löhr ◽  
Natalia Rogova ◽  
Volker Dötsch ◽  
Vladimir V. Rogov
Keyword(s):  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Biochemical Characterization ◽  
Effective Interaction ◽  
Regulatory Region ◽  
Titration Calorimetry ◽  
Enzymatic Reactions ◽  
Cellular Processes ◽  
Mechanism Of Interaction

Ubiquitin fold modifier 1 (UFM1) is a member of the ubiquitin-like protein family. UFM1 undergoes a cascade of enzymatic reactions including activation by UBA5 (E1), transfer to UFC1 (E2) and selective conjugation to a number of target proteins via UFL1 (E3) enzymes. Despite the importance of ufmylation in a variety of cellular processes and its role in the pathogenicity of many human diseases, the molecular mechanisms of the ufmylation cascade remains unclear. In this study we focused on the biophysical and biochemical characterization of the interaction between UBA5 and UFC1. We explored the hypothesis that the unstructured C-terminal region of UBA5 serves as a regulatory region, controlling cellular localization of the elements of the ufmylation cascade and effective interaction between them. We found that the last 20 residues in UBA5 are pivotal for binding to UFC1 and can accelerate the transfer of UFM1 to UFC1. We solved the structure of a complex of UFC1 and a peptide spanning the last 20 residues of UBA5 by NMR spectroscopy. This structure in combination with additional NMR titration and isothermal titration calorimetry experiments revealed the mechanism of interaction and confirmed the importance of the C-terminal unstructured region in UBA5 for the ufmylation cascade.

scholarly journals Zebrafish Models of Autosomal Recessive Ataxias

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 836
Author(s):  
Ana Quelle-Regaldie ◽  
Daniel Sobrido-Cameán ◽  
Antón Barreiro-Iglesias ◽  
María Jesús Sobrido ◽  
Laura Sánchez
Keyword(s):  
Animal Models ◽  
Autosomal Recessive ◽  
Molecular Mechanisms ◽  
System Development ◽  
Rapid Development ◽  
Nervous System Development ◽  
Central Nervous System Development ◽  
Cellular Processes ◽  
Recessive Disorders

Autosomal recessive ataxias are much less well studied than autosomal dominant ataxias and there are no clearly defined systems to classify them. Autosomal recessive ataxias, which are characterized by neuronal and multisystemic features, have significant overlapping symptoms with other complex multisystemic recessive disorders. The generation of animal models of neurodegenerative disorders increases our knowledge of their cellular and molecular mechanisms and helps in the search for new therapies. Among animal models, the zebrafish, which shares 70% of its genome with humans, offer the advantages of being small in size and demonstrating rapid development, making them optimal for high throughput drug and genetic screening. Furthermore, embryo and larval transparency allows to visualize cellular processes and central nervous system development in vivo. In this review, we discuss the contributions of zebrafish models to the study of autosomal recessive ataxias characteristic phenotypes, behavior, and gene function, in addition to commenting on possible treatments found in these models. Most of the zebrafish models generated to date recapitulate the main features of recessive ataxias.

scholarly journals The Chinese Medicinal Formulation Guzhi Zengsheng Zhitongwan Modulates Chondrocyte Structure, Dynamics, and Metabolism by Controlling Multiple Functional Proteins

2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Baojin Yao ◽  
Bocheng Lu ◽  
Mei Zhang ◽  
Hongwei Gao ◽  
Xiangyang Leng ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Research Field ◽  
Medical Systems ◽  
Cellular Processes ◽  
Structure Dynamics ◽  
National Medical ◽  
Medicinal Formulation

Traditional Chinese medicine is one of the oldest medical systems in the world and has its unique principles and theories in the prevention and treatment of human diseases, which are achieved through the interactions of different types of materia medica in the form of Chinese medicinal formulations. GZZSZTW, a classical and effective Chinese medicinal formulation, was designed and created by professor Bailing Liu who is the only national medical master professor in the clinical research field of traditional Chinese medicine and skeletal diseases. GZZSZTW has been widely used in clinical settings for several decades for the treatment of joint diseases. However, the underlying molecular mechanisms are still largely unknown. In the present study, we performed quantitative proteomic analysis to investigate the effects of GZZSZTW on mouse primary chondrocytes using state-of-the-art iTRAQ technology. We demonstrated that the Chinese medicinal formulation GZZSZTW modulates chondrocyte structure, dynamics, and metabolism by controlling multiple functional proteins that are involved in the cellular processes of DNA replication and transcription, protein synthesis and degradation, cytoskeleton dynamics, and signal transduction. Thus, this study has expanded the current knowledge of the molecular mechanism of GZZSZTW treatment on chondrocytes. It has also shed new light on possible strategies to further prevent and treat cartilage-related diseases using traditional Chinese medicinal formulations.

Structure, Function, Involvement in Diseases and Targeting of 14-3-3 Proteins: An Update

2018 ◽  
Vol 25 (1) ◽  
pp. 5-21 ◽  
Author(s):  
Ylenia Cau ◽  
Daniela Valensin ◽  
Mattia Mori ◽  
Sara Draghi ◽  
Maurizio Botta
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Specific Protein ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Protein Partners ◽  
High Sequence Homology ◽  
Small Molecule Modulators

14-3-3 is a class of proteins able to interact with a multitude of targets by establishing protein-protein interactions (PPIs). They are usually found in all eukaryotes with a conserved secondary structure and high sequence homology among species. 14-3-3 proteins are involved in many physiological and pathological cellular processes either by triggering or interfering with the activity of specific protein partners. In the last years, the scientific community has collected many evidences on the role played by seven human 14-3-3 isoforms in cancer or neurodegenerative diseases. Indeed, these proteins regulate the molecular mechanisms associated to these diseases by interacting with (i) oncogenic and (ii) pro-apoptotic proteins and (iii) with proteins involved in Parkinson and Alzheimer diseases. The discovery of small molecule modulators of 14-3-3 PPIs could facilitate complete understanding of the physiological role of these proteins, and might offer valuable therapeutic approaches for these critical pathological states.

Desiccation-tolerance specific gene expression in leaf tissue of the resurrection plant Sporobolus stapfianus

2007 ◽  
Vol 34 (7) ◽  
pp. 589 ◽  
Author(s):  
Tuan Ngoc Le ◽  
Cecilia K. Blomstedt ◽  
Jianbo Kuang ◽  
Jennifer Tenlen ◽  
Donald F. Gaff ◽  
...  
Keyword(s):  
Drought Stress ◽  
Desiccation Tolerance ◽  
Molecular Mechanisms ◽  
Leaf Tissue ◽  
Resurrection Plant ◽  
Specific Gene ◽  
Irreversible Damage ◽  
Cellular Processes ◽  
Sporobolus Stapfianus ◽  
Normal Metabolism

The desiccation tolerant grass Sporobolus stapfianus Gandoger can modulate cellular processes to prevent the imposition of irreversible damage to cellular components by water deficit. The cellular processes conferring this ability are rapidly attenuated by increased water availability. This resurrection plant can quickly restore normal metabolism. Even after loss of more than 95% of its total water content, full rehydration and growth resumption can occur within 24 h. To study the molecular mechanisms of desiccation tolerance in S. stapfianus, a cDNA library constructed from dehydration-stressed leaf tissue, was differentially screened in a manner designed to identify genes with an adaptive role in desiccation tolerance. Further characterisation of four of the genes isolated revealed they are strongly up-regulated by severe dehydration stress and only in desiccation-tolerant tissue, with three of these genes not being expressed at detectable levels in hydrated or dehydrating desiccation-sensitive tissue. The nature of the putative proteins encoded by these genes are suggestive of molecular processes associated with protecting the plant against damage caused by desiccation and include a novel LEA-like protein, and a pore-like protein that may play an important role in peroxisome function during drought stress. A third gene product has similarity to a nuclear-localised protein implicated in chromatin remodelling. In addition, a UDPglucose glucosyltransferase gene has been identified that may play a role in controlling the bioactivity of plant hormones or secondary metabolites during drought stress.

scholarly journals NAD+Metabolism in Aging and Cancer

2019 ◽  
Vol 3 (1) ◽  
pp. 105-130 ◽  
Author(s):  
Tyler G. Demarest ◽  
Mansi Babbar ◽  
Mustafa N. Okur ◽  
Xiuli Dan ◽  
Deborah L. Croteau ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Accelerated Aging ◽  
Cancer Therapies ◽  
Nad Metabolism ◽  
Cellular Processes ◽  
Cancer Pathogenesis ◽  
Nicotinamide Mononucleotide ◽  
Age Related

Aging is a major risk factor for many types of cancer, and the molecular mechanisms implicated in aging, progeria syndromes, and cancer pathogenesis display considerable similarities. Maintaining redox homeostasis, efficient signal transduction, and mitochondrial metabolism is essential for genome integrity and for preventing progression to cellular senescence or tumorigenesis. NAD+is a central signaling molecule involved in these and other cellular processes implicated in age-related diseases and cancer. Growing evidence implicates NAD+decline as a major feature of accelerated aging progeria syndromes and normal aging. Administration of NAD+precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) offer promising therapeutic strategies to improve health, progeria comorbidities, and cancer therapies. This review summarizes insights from the study of aging and progeria syndromes and discusses the implications and therapeutic potential of the underlying molecular mechanisms involved in aging and how they may contribute to tumorigenesis.

scholarly journals Energetics and mammary carcinogenesis: effects of moderate-intensity running and energy intake on cellular processes and molecular mechanisms in rats

2009 ◽  
Vol 106 (3) ◽  
pp. 911-918 ◽  
Author(s):  
Zongjian Zhu ◽  
Weiqin Jiang ◽  
John N. McGinley ◽  
Henry J. Thompson
Keyword(s):  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Mammary Carcinogenesis ◽  
Mitochondrial Pathway ◽  
Moderate Intensity ◽  
Free Access ◽  
Sprague Dawley ◽  
Cellular Processes ◽  
Sprague Dawley Rats ◽  
Induced Apoptosis

The objective of this experiment was to determine the effects on mammary carcinogenesis of similar limitations in energy availability either by energy expenditure due to moderate-intensity running (physical activity, PA) or by regulating dietary energy (RE) intake relative to a sedentary control (SC) group that ate ad libitum. A total of 90 female Sprague-Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter were randomized to either SC, a PA group given free access to a motorized running wheel, or a RE group whose food intake limited growth to the rate observed in PA. Compared with SC, mammary carcinogenesis was inhibited by RE or PA. Cancer incidence, 92.6%, 77.8%, and 66.7% ( P = 0.06), and cancer multiplicity, 3.44, 2.11, and 1.62 cancers/rat ( P = 0.006), in SC, RE, and PA, respectively, were reduced to a similar extent by RE and PA. Histological and Western blot analyses of mammary carcinomas provided evidence that RE and PA induced apoptosis via the mitochondrial pathway, that cell cycle progression was suppressed at the G1/S transition, and that intratumoral blood vessel density was reduced, although it remains to be determined whether PA and RE exert these effects via the same mechanisms.

scholarly journals Profiling Cellular Processes in Adipose Tissue during Weight Loss Using Time Series Gene Expression

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 525 ◽  
Author(s):  
Samar Tareen ◽  
Michiel Adriaens ◽  
Ilja Arts ◽  
Theo de Kok ◽  
Roel Vink ◽  
...  
Keyword(s):  
Gene Expression ◽  
Time Series ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Dietary Intervention ◽  
Network Biology ◽  
Analysis Tool ◽  
Cellular Processes ◽  
Time Series Gene Expression

Obesity is a global epidemic identified as a major risk factor for multiple chronic diseases and, consequently, diet-induced weight loss is used to counter obesity. The adipose tissue is the primary tissue affected in diet-induced weight loss, yet the underlying molecular mechanisms and changes are not completely deciphered. In this study, we present a network biology analysis workflow which enables the profiling of the cellular processes affected by weight loss in the subcutaneous adipose tissue. Time series gene expression data from a dietary intervention dataset with two diets was analysed. Differentially expressed genes were used to generate co-expression networks using a method that capitalises on the repeat measurements in the data and finds correlations between gene expression changes over time. Using the network analysis tool Cytoscape, an overlap network of conserved components in the co-expression networks was constructed, clustered on topology to find densely correlated genes, and analysed using Gene Ontology enrichment analysis. We found five clusters involved in key metabolic processes, but also adipose tissue development and tissue remodelling processes were enriched. In conclusion, we present a flexible network biology workflow for finding important processes and relevant genes associated with weight loss, using a time series co-expression network approach that is robust towards the high inter-individual variation in humans.

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