Abstract：
:We report the results of computational modeling of a three-dimensional all-atom structure of the membrane-associated protein encoded by the NAT8L gene, aspartate N-acetyltransferase, which is essential for brain synthesis of N-acetyl-l-aspartate (NAA). The lack of experimentally derived three-dimensional structures of NAT8L poses one of the obstacles in studies of the mechanism of NAA formation and understanding the precise role of NAA in neurological disorders. We apply a computational protocol employing the contact map prediction, ab initio folding, homology modeling, and refinement to obtain a structure of NAT8L with the aspartate and acetyl coenzyme A cofactors in the protein molecule. To verify the computational protocol, we check its predictive power by reproducing the crystal structure of a related N-acetyltransferase domain, specifically, that from the bacterial N-acetylglutamate synthase. We show that the constructed NAT8L model correlates with structural features of the protein revealed in rare experimental studies. The obtained structure of the enzyme active site with the trapped reactants suggests a mechanism of the acetyl transfer upon NAA formation.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Polyakov IV,Kniga AE,Grigorenko BL,Nemukhin AVdoi
10.1021/acschemneuro.0c00250subject
Has Abstractpub_date
2020-08-05 00:00:00pages
2296-2302issue
15issn
1948-7193journal_volume
11pub_type
杂志文章abstract：:In our efforts to develop hybrid compounds of curcumin and melatonin as potential disease-modifying agents for Alzheimer's disease (AD), a potent lead hybrid compound, Z-CM-I-1, has been recently identified and biologically characterized in vitro. In this work, we report the in vivo effects of Z-CM-I-1 on AD pathologi...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.5b00082
更新日期：2015-08-19 00:00:00
abstract：:Neurotrophins, as important regulators of neural development, function, and survival, have a therapeutic potential to repair damaged neurons. However, a controlled delivery of therapeutic molecules to injured tissue remains one of the greatest challenges facing the translation of novel drug therapeutics field. This st...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn400080h
更新日期：2013-09-18 00:00:00
abstract：:The accumulation and deposition of fibrillar aggregates of α-synuclein (α-syn) into Lewy bodies are the major hallmarks of Parkinson's disease (PD) for which there is no cure yet. Disrupting preformed α-syn fibrils is considered one of the rational therapeutic strategies to combat PD. Experimental studies reported tha...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00598
更新日期：2020-12-16 00:00:00
abstract：:Alzheimer's disease is a progressive neurodegenerative disorder that mainly affects the elderly. Soluble β-amyloid oligomer, which can induce neurotoxicity, is generally regarded as the main neurotoxin in Alzheimer's disease. Here we report that eckmaxol, a phlorotannin extracted from the brown alga Ecklonia maxima, c...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00527
更新日期：2018-06-20 00:00:00
abstract：:Early diagnosis in Alzheimer's disease (AD), prior to the appearance of marked clinical symptoms, is critical to prevent irreversible neuronal damage and neural malfunction that lead to dementia and death. Therefore, there is an urgent need to generate new contrast agents which reveal by a noninvasive method the prese...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00260
更新日期：2018-05-16 00:00:00
abstract：:Recent clinical approvals of brain imaging radiotracers targeting amyloid-β provided clinicians the tools to detect and confirm Alzheimer's disease pathology without autopsy or biopsy. While current imaging agents are effective in postsymptomatic Alzheimer's patients, there is much room for improvement in earlier diag...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00093
更新日期：2019-06-19 00:00:00
abstract：:Dendritic spines are the postsynaptic sites for the majority of excitatory synapses in the mammalian forebrain. While many spines display great stability, others change shape in a matter of seconds to minutes. These rapid alterations in dendritic spine number and size require tight control of the actin cytoskeleton, t...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn100012x
更新日期：2010-05-19 00:00:00
abstract：:Myasthenia gravis (MG) is an autoimmune T cell-dependent B cell-mediated disorder of the neuromuscular junction (NMJ) characterized by fluctuating skeletal muscle weakness, most commonly attributed to pathogenic autoantibodies against postsynaptic nicotinic acetylcholine receptors (AChRs). Although MG pathogenesis is ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00678
更新日期：2020-03-04 00:00:00
abstract：:Carboranes have been extensively investigated as potential drugs for the treatment of malignant human brain tumors by boron neutron capture therapy (BNCT). This noninvasive treatment modality utilizes compounds containing the nonradioactive isotope 10B which has a high propensity to capture slow neutrons. In response,...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00512
更新日期：2019-03-20 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00570
更新日期：2020-10-07 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/acschemneuro.8b00151
更新日期：2018-06-20 00:00:00
abstract：:The abnormal aggregation of α-synuclein (α-Syn) is closely associated with Parkinson's disease. Different post-translational modifications of α-Syn have been identified and contribute distinctly in α-Syn aggregation and cytotoxicity. Recently, α-Syn was reported to be N-terminally acetylated in cells, yet the function...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00250
更新日期：2017-10-18 00:00:00
abstract：:Tropomyosin receptor kinases (TrkA/B/C) are critically involved in the development of the nervous system, in neurological disorders as well as in multiple neoplasms of both neural and non-neural origins. The development of Trk radiopharmaceuticals would offer unique opportunities toward a more complete understanding o...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn500193f
更新日期：2015-02-18 00:00:00
abstract：:The molecular mechanism of protein aggregation is of both fundamental and clinical importance as amyloid aggregates are linked to a number of neurodegenerative disorders. Such protein aggregates include macroscopic insoluble fibrils as well as small soluble oligomeric species. Time-dependent resolution of these specie...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00250
更新日期：2018-12-19 00:00:00
abstract：:Lithium has been used for the treatment of mood disorders for decades though the molecular mechanism of its therapeutic action and intracellular targets remain furtive. We report that neurotropic agent Li+ binds to the neuronal calcium sensor, Downstream Regulatory Element Antagonist Modulator (DREAM), with an equilib...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00399
更新日期：2020-09-02 00:00:00
abstract：:Currently, anti-AD drug discovery using target-based approaches is extremely challenging due to unclear etiology of AD and absence of validated therapeutic protein targets. Neuronal death, regardless of causes, plays a key role in AD progression, and it is directly linked to neuroinflammation. Meanwhile, phenotypic sc...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.6b00125
更新日期：2016-11-16 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00161
更新日期：2020-05-06 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.6b00091
更新日期：2016-04-20 00:00:00
abstract：:Tau aggregation in neuronal cells has recently received significant attention as a robust predictor of the progression of Alzheimer's disease (AD) because of its proven correlation with the degree of cognitive impairment in AD patients. Accordingly, noninvasive imaging of tau aggregates has been highlighted as a promi...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00224
更新日期：2017-10-18 00:00:00
abstract：:Effective therapies for glioblastoma multiforme (GBM) are not currently available. A small molecule has been identified using fragment-based drug-discovery guided by NMR that targets important protein-protein interactions controlling GBM invasion and pathogenicity. This first generation drug displays excellent pharmac...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
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更新日期：2019-03-20 00:00:00
abstract：:The glycine receptor (GlyR) is a ligand-activated chloride channel, whose mutations are the major cause of hereditary hyperekplexia. The hyperekplexia-causing R271Q mutation, which is located at the extracellular outer mouth of the channel pore, dramatically impairs the GlyR function manifesting a reduced sensitivity ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00522
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journal_title：ACS chemical neuroscience
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更新日期：2020-03-18 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn500337u
更新日期：2015-04-15 00:00:00
abstract：:The present study was performed to investigate the possible role of protein kinase C (PKC) in morphine tolerance at spinal levels of rats. Intrathecal injection of 10 μg of morphine induced increases in the hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation in rats. After intrathecal inject...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn900005d
更新日期：2010-02-17 00:00:00
abstract：:The melanocortin system regulates an array of diverse physiological functions including pigmentation, feeding behavior, energy homeostasis, cardiovascular regulation, sexual function, and steroidogenesis. Endogenous melanocortin agonist ligands all possess the minimal messaging tetrapeptide sequence His-Phe-Arg-Trp. B...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00181
更新日期：2018-11-21 00:00:00
abstract：:Natural environments contain numerous volatile compounds emanating from a large number of sources, and the survival of many animals depends on their ability to segregate odors of interest within complex odorous scenes. In a recent paper, we described how the ability of mice to detect odors within mixtures depends on t...
journal_title：ACS chemical neuroscience
pub_type： 评论,杂志文章
doi：10.1021/cn500199n
更新日期：2014-10-15 00:00:00
abstract：:Exposure to di-(2-ethylhexyl) phthalate (DEHP), a widely used kind of plasticizer, can result in neurodevelopment impairments and learning and memory disorders. We studied the effects and possible mechanisms of maternal DEHP treatment on hippocampal synaptic plasticity in offspring. Pregnant Wistar rats were randomly ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00612
更新日期：2021-01-20 00:00:00
abstract：:Glioblastoma (GBM) is characterized by a poor response to conventional chemotherapeutic agents, attributed to the insurgence of drug resistance mechanisms and to the presence of a subpopulation of glioma stem cells (GSCs). GBM cells and GSCs present, among others, an overexpression of antiapoptotic proteins and an inh...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00023
更新日期：2018-01-17 00:00:00
abstract：:The transporters for the neurotransmitters serotonin and dopamine (SERT and DAT, respectively) are targets for drugs used in the treatment of mental disorders and widely used drugs of abuse. Studies of prokaryotic homologues have advanced our structural understanding of SERT and DAT, but it still remains enigmatic whe...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.6b00164
更新日期：2016-10-19 00:00:00
abstract：:We review here recent discoveries in the exciting new field of neuromicrobiology. This field encompasses the interactions between the microbiome and the central nervous system. The microbiome has a tremendous impact on human health. In particular, the gut microbiota may play a key role in many essential processes in h...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/acschemneuro.7b00373
更新日期：2018-02-21 00:00:00
