Abstract：
AIM:Based on the structural analysis to reveal the mechanism of ligand binding to beta-secretase and the specificity of each binding sub-site. METHODS:Molecular dynamics was used to simulate on the ligand free beta-secretase and ligand bound beta-secretase. The trajectories were analyzed using the essential dynamics, and the significant conformational change was illustrated employing the DynDom program. RESULTS:The essential dynamics and DynDom analyses clearly showed that the beta-secretase experienced a large conformational change upon the substrate or inhibitor binding. The flap structure adopted a swing motion, gradually covering the active site to facilitate the ligand binding process. Residues Ser86 and Ile87 served as the hinge point. Inhibitor-enzyme interaction analysis revealed that residues at P2, P1, and P1' positions of the inhibitor were very important for the binding, and residues at P2' and P3' positions may be modified to improve the binding specificity. S3 subsite of the enzyme still had space to modify the inhibitors in increasing the binding affinity. CONCLUSION:The information presented here is valuable and could be used to identify small molecular inhibitors of beta-secretase.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Xiong B,Huang XQ,Shen LL,Shen JH,Luo XM,Shen X,Jiang HL,Chen KXsubject
Has Abstractpub_date
2004-06-01 00:00:00pages
705-13issue
6eissn
1671-4083issn
1745-7254journal_volume
25pub_type
杂志文章abstract：AIM:To examine the role of atorvastatin on volume-overload-induced heart failure and to test the hypothesis that atorvastatin inhibits MMP-2 and 9 expression in heart failure with non-ischemic etiology. METHODS:Arteriovenous (AV) fistula-treated rats were administered with atorvastatin (3 mg/kg/d) or vehicle for 17 we...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00515.x
更新日期：2007-04-01 00:00:00
abstract：:A variety of cardiovascular diseases is accompanied by the loss of vascular contractility. This study sought to investigate the effects of curcumin, a natural polyphenolic compound present in turmeric, on mouse vascular contractility and the underlying mechanisms. After mice were administered curcumin (100 mg·kg-1·d-1...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2017.18
更新日期：2017-10-01 00:00:00
abstract：AIM:alpha2 nAChR subunit mRNA expression in mice is most intense in the olfactory bulbs and interpeduncular nucleus. We aimed to investigate the properties of alpha2* nAChRs in these mouse brain regions. METHODS:alpha2 nAChR subunit-null mutant mice were engineered. Pharmacological and immunoprecipitation studies were...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2009.68
更新日期：2009-06-01 00:00:00
abstract：AIM:To study the influence of angiotensin (Ang) II receptor antagonist (AT1) valsartan and angiotensin-converting enzyme (ACE) inhibitor fosinopril on the cardiac hypertrophy induced by catecholamine. METHODS:A cardiac hypertrophy model was produced by i.p. norepinephrine (NE) 1.5 mg.kg-1.d-1 x 15 d. The animals were ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2000-09-01 00:00:00
abstract：AIM:To investigate the actions of the muscarinic agonist carbachol on glutamate-induced neurotoxicity in PC12 cells, and the underlying mechanisms. METHODS:PC12 cells were treated with different concentrations of glutamate for 24 or 48 h. The cell viability was measured using MTT assay, and the expression and activati...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2013.42
更新日期：2013-07-01 00:00:00
abstract：AIM:To develop a robust, cell-based, high-content screening (HCS) assay based on receptor internalization for the identification of novel modulators of the epidermal growth factor receptor (EGFR). METHODS:Agonist-induced receptor internalization is part of the signaling cascade of EGFR. Fluorescent-tagged epidermal gr...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00640.x
更新日期：2007-10-01 00:00:00
abstract：AIM:Epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent in green tea. The aim of this study is to investigate the effects of EGCG on proliferation and migration of the human colon cancer SW620 cells. METHODS:Proliferation and migration of SW620 cells were induced by the protease-activated receptor ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.139
更新日期：2012-01-01 00:00:00
abstract：AIM:To investigate the effect of Ginkgolide B (GB) on action potential (AP), delayed rectifier potassium current (IK), and L-type calcium current (I(Ca-L)) in guinea pig ventricular myocytes. METHODS:Single ventricular myocytes were isolated by an enzymatic dissociation method. AP, IK, I(Ca-L) were recorded by whole-c...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-02-01 00:00:00
abstract：AIM:To study wound healing activity of the human placental extract (HPE) in rats. METHODS:Full thickness wounds were inflicted on depilated dorsum of Charles foster rats with 8 mm Acu-punch biopsy. The HPE was applied both at topical and im routes (2.5 mL/kg). Effects were compared on the basis of physical criteria, b...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2001-12-01 00:00:00
abstract：:Excessive and abnormal vessel growth plays a critical role in the pathogenesis of many diseases, such as cancer. Angiogenesis is one of the hallmarks of cancer growth, invasion, and metastasis. Discovery of novel antiangiogenic agents would provide new insights into the mechanisms of angiogenesis, as well as potential...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-019-0224-x
更新日期：2019-11-01 00:00:00
abstract：:Breast cancer resistance protein (BCRP) is one of ATP-binding cassette (ABC) transporters in brain microvessel endothelial cells that transport their substrates from brain to blood, thus limiting substrates to crossing into brain through blood-brain barrier. Our previous works show that bile duct ligation (BDL) impair...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-019-0242-8
更新日期：2020-02-01 00:00:00
abstract：AIM:Apolipoprotein E (ApoE) plays an important role in the transport and metabolism of lipids. Recent studies show that bone mass is increased in young apoE(-/-) mice. In this study we investigated the bone phenotype and metabolism in aged apoE(-/-) mice. METHODS:Femurs and tibias were collected from 18- and 72-week-o...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2015.95
更新日期：2015-12-01 00:00:00
abstract：AIM:Using sparse data of valproate (VPA) serum concentrations to build a population pharmacokinetic (PPK) model of VPA in Chinese children with epilepsy and to predict serum concentrations for new patients using a Bayesian approach. METHODS:Two hundred epileptic children, whose VPA serum concentrations were collected,...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-12-01 00:00:00
abstract：:Brain and eye tissues are subject to a reduced version of immune surveillance, which has evolved to protect the particularly sensitive tissues from accidental bystander damage created by regular inflammatory responses. Yet, there are autoimmune diseases in both organs. This review discusses the nature of immune reacti...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2010.149
更新日期：2010-09-01 00:00:00
abstract：AIM:Genetic variation in ALOX12, which encoded human 12-lipoxygenase, was found to be associated with fat mass in young Chinese men. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) and haplotypes in the ALOX15 gene and obesity-related phenotypes in Chinese ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.167
更新日期：2012-02-01 00:00:00
abstract：AIM:To construct a recombinant adenovirus that can express human spermidine/ spermine N1-acetyltransferase (SSAT) and detect its inhibitory effect on colorectal cancer cell growth in vitro. METHODS:A 516 bp cDNA of SSAT was amplified and cloned into a pGL3-hTERT plasmid. The pGL3-hTERT-SSAT recombinant was digested, a...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00779.x
更新日期：2008-05-01 00:00:00
abstract：:Type 2 diabetes (T2D) and Alzheimer's disease (AD) share several common pathophysiological features. Huperzine A (Hup A), a Lycopodium alkaloid extracted from the Chinese herb moss Huperzia serrata, is a specific and reversible inhibitor of acetylcholinesterase, which is clinically used for the treatment of AD. In thi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-019-0257-1
更新日期：2020-02-01 00:00:00
abstract：:Emerging evidence demonstrates that a c-Met antibody-drug conjugate (ADC) has superior efficacy and safety profiles compared with those of currently available small molecules or antibody inhibitors for the treatment of c-Met-overexpressing cancers. Here we described both the in vitro and in vivo efficacies of SHR-A140...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-018-0198-0
更新日期：2019-07-01 00:00:00
abstract：AIM:To investigate the effect of tricyclodecane-9-yl-xanthogenate (D609) on cell differentiation in vascular endothelial cells (VECs) and marrow stromal cells (MSCs). METHODS:Morphological changes were observed under phase contrast microscope. Electron microscope and immunostaining were used for VECs identification. T...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-04-01 00:00:00
abstract：AIM:To investigate the effects of 3-n-butylphthalide (NBP) on apoptosis induced by transient focal cerebral ischemia in rats, compare the action potency of s-(-)-, r-(+)- and (+/-)-NBP, and clarify the enantiomer that played a main role. METHODS:DNA fragmentation was detected by the terminal deoxynucleotidyl transfera...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2003-08-01 00:00:00
abstract：:It was reported that antituberculosis medicines could induce liver damage via oxidative stress. In this study, we investigated the effects of rifampicin (RFP) on the membrane expression of multidrug resistance-associated protein 2 (MRP2) and the relationship between oxidative stress and RFP-induced endocytosis of MRP2...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-019-0266-0
更新日期：2020-01-01 00:00:00
abstract：:Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2015.73
更新日期：2015-10-01 00:00:00
abstract：AIM:The aim of this study was to study the effects of compound FLZ, a novel cyclic derivative of squamosamide from Annona glabra, on brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element-binding protein (CREB) signaling and neuronal apoptosis in the hippocampus of the amylo...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.3
更新日期：2010-03-01 00:00:00
abstract：AIM:The conventional method for analyzing 24-h ambulatory blood pressure monitoring (24-h ABPM) is insufficient to deal with the large amount of data collected. The aim of this study was to develop a novel cyclic fluctuation model for 24-h ABPM in Chinese patients with mild to moderate hypertension. METHODS:The data w...
journal_title：Acta pharmacologica Sinica
pub_type： 临床试验,杂志文章
doi：10.1038/aps.2013.45
更新日期：2013-08-01 00:00:00
abstract：AIM:To explore the action mechanism of antidepressants. METHODS:The PC12 cell proliferation was detected by flow cytometry. The proliferation of hippocampal progenitor cells and level of brain-derived neurotrophic factor (BDNF) were measured by immunohistochemistry. RESULTS:Treatment with N-methylaspartate (NMDA) 600...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-11-01 00:00:00
abstract：AIM:To observe the effects of tripcholorolide (T4) on inflammatory reaction of mouse alveolar macrophages. METHODS:RT-PCR was used to investigate tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), IL-6, IL-10, and inducible nitric-oxide synthase (iNOS) mRNA expression in alveolar macrophages afte...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2000-12-01 00:00:00
abstract：AIM:To develop and validate a novel precolumn derivatization method for the quantitative determination and pharmacokinetic application of acetylshikonin in macaque monkeys by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). METHODS:2-Mercaptoethanol was added to the blood sample a...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00898.x
更新日期：2008-12-01 00:00:00
abstract：AIM:To investigate molecular mechanism of testis development and spermatogenesis. METHODS:A human testis cDNA microarray was hybridized with probes from human adult testis, embryo testis and human sperm, and the differential expressed clones were sequenced and analyzed. Expression of PIAS-NY gene was analyzed by RT-PC...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-08-01 00:00:00
abstract：:Volatile anesthetics improve postischemic cardiac function and reduce infarction even when administered for only a brief time at the onset of reperfusion. A recent study showed that sevoflurane postconditioning (SPC) attenuated myocardial reperfusion injury, but the underlying mechanisms remain unclear. In this study,...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-018-0066-y
更新日期：2019-01-01 00:00:00
abstract：AIM:To evaluate the pharmacokinetics of L-threonate after single or multiple oral administrations and its safety profile in healthy Chinese volunteers. METHODS:This was an open-label, single- and multiple-dose study. The subjects were assigned to receive a single dose, 675, 2025, or 4050 mg, of calcium L-threonate (n=...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.138
更新日期：2011-12-01 00:00:00
