Abstract：
:As an important target for the development of novel antibiotics, UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) has been widely studied. Pyridone methylsulfone hydroxamate (PMH) compounds can effectively inhibit the catalytic activity of LpxC. In this work, the three-dimensional quantitative structure-activity relationships of PMH inhibitors were explored and models with good predictive ability were established using comparative molecular field analysis and comparative molecular similarity index analysis methods. The effect of PMH inhibitors' electrostatic potential on the inhibitory ability of Pseudomonas aeruginosa LpxC (PaLpxC) is revealed at the molecular level via molecular electrostatic potential analyses. Then, two molecular dynamics simulations for the PaLpxC and PaLpxC-inhibitor systems were also performed respectively to investigate the key residues of PaLpxC hydrolase binding to water molecules. The results indicate that orderly alternative water molecules can form stable hydrogen bonds with M62, E77, T190, and H264 in the catalytic center, and tetracoordinate to zinc ion along with H78, H237, and D241. It was found that the conformational transition space of PaLpxC changes after association with PMH inhibitors through free energy landscape and cluster analyses. Finally, a possible inhibitory mechanism of PMH inhibitors was proposed, based on our molecular simulation. This paper will provide a theoretical basis for the molecular design of LpxC-targeting antibiotics.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Zuo K,Liang L,Du W,Sun X,Liu W,Gou X,Wan H,Hu Jdoi
10.3390/ijms18050761subject
Has Abstractpub_date
2017-05-06 00:00:00issue
5issn
1422-0067pii
ijms18050761journal_volume
18pub_type
杂志文章abstract：:Soybean mosaic virus (SMV) is one of the most prevalent and important pathogens of soybean, which produces 11 proteins, and the third protein, P3, was suggested to be involved in virus movement and replication, as well as host infection. During the virus infection, host proteins are essential in the virus cycle. Howev...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20143388
更新日期：2019-07-10 00:00:00
abstract：:Updated measurements of charged particle fluxes during the transit from Earth to Mars as well as on site measurements by Curiosity of Martian surface radiation fluxes identified potential health hazards associated with radiation exposure for human space missions. Designing mitigation strategies of radiation risks to a...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20010176
更新日期：2019-01-05 00:00:00
abstract：:Virtual screening consists of using computational tools to predict potentially bioactive compounds from files containing large libraries of small molecules. Virtual screening is becoming increasingly popular in the field of drug discovery as in silico techniques are continuously being developed, improved, and made ava...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20061375
更新日期：2019-03-19 00:00:00
abstract：:Diabetic retinopathy (DR), a sight-threatening neurovasculopathy, is the leading cause of irreversible blindness in the developed world. DR arises as the result of prolonged hyperglycemia and is characterized by leaky retinal vasculature, retinal ischemia, retinal inflammation, angiogenesis, and neovascularization. Th...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20194755
更新日期：2019-09-25 00:00:00
abstract：:Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms17040490
更新日期：2016-04-02 00:00:00
abstract：:Salmonella typhimurium cells were subjected to pulsed electric field (PEF) treatment at 25 kV/cm for 0-4 ms to investigate the effect of PEF on the cytoplasmic membrane lipids and oxidative injury of cells. Results indicated that PEF treatment induced a decrease of membrane fluidity of Salmonella typhimurium (S. typhi...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms17081374
更新日期：2016-08-22 00:00:00
abstract：:In general, a drug candidate is evaluated using 2D-cultured cancer cells followed by an animal model. Despite successful preclinical testing, however, most drugs that enter human clinical trials fail. The high failure rates are mainly caused by incompatibility between the responses of the current models and humans. He...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18112348
更新日期：2017-11-07 00:00:00
abstract：:In addition to its role in ribosome biogenesis, ribosomal protein S3 (RPS3), a component of the 40S ribosomal subunit, has been suggested to possess several extraribosomal functions, including an apoptotic function. In this study, we demonstrated that in the mouse brain, the protein levels of RPS3 were altered by the ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19092723
更新日期：2018-09-12 00:00:00
abstract：:In this study, new composite bisphosphonate delivery systems were obtained from polyurethanes (PUs) and nanocrystalline hydroxyapatite (HA). The biodegradable PUs were first synthesized from poly(ε-caprolactone) diols (PCL diols), poly(ethylene adipate) diol, 1,6-hexamethylene diisocyanate, 1,4-butanediol and HA. More...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms150916831
更新日期：2014-09-22 00:00:00
abstract：:Chemokines (C-X-C) motif ligand (CXCL) 5 and 8 are overexpressed in patients with multiple sclerosis, where CXCL5 serum levels were shown to correlate with blood-brain barrier dysfunction as evidenced by gadolinium-enhanced magnetic resonance imaging. Here, we studied the potential role of CXCL5/CXCL8 receptor 2 (CXCR...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20030602
更新日期：2019-01-30 00:00:00
abstract：:The lack of effective Alzheimer's disease treatment is becoming a challenge for researchers and prompts numerous attempts to search for and develop better therapeutic solutions. Compounds that affect several routes of the neurodegeneration cascade leading to the development of disease are of particular interest. An ex...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21082749
更新日期：2020-04-15 00:00:00
abstract：:RNA editing aims to treat genetic disease through altering gene expression at the transcript level. Pairing site-directed RNA-targeting mechanisms with engineered deaminase enzymes allows for the programmable correction of G>A and T>C mutations in RNA. This offers a promising therapeutic approach for a range of geneti...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21030777
更新日期：2020-01-25 00:00:00
abstract：:Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, mainly affecting the elderly. The disease progresses gradually, with core motor presentations and a multitude of non-motor manifestations. There are two neuropathological hallmarks of PD, the dopaminergic neuronal loss and the alp...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20215312
更新日期：2019-10-25 00:00:00
abstract：:Attributed to the tropism for host microvascular endothelium lining the blood vessels, vascular inflammation and dysfunction represent salient features of rickettsial pathogenesis, yet the details of fundamentally important pathogen interactions with host endothelial cells (ECs) as the primary targets of infection rem...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21197179
更新日期：2020-09-29 00:00:00
abstract：:PCSK9 (Proprotein convertase subtilisin/kexin type 9) increases plasma cholesterol levels by promoting LDL receptor degradation. Current antibody inhibitors block the interaction between PCSK9 and LDL receptors, significantly decrease plasma cholesterol levels, and provide beneficial clinical outcomes. To reduce the a...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19020640
更新日期：2018-02-24 00:00:00
abstract：:Biomarkers for the early detection of pancreatic cancer are urgently needed. The aim of this pilot study was to evaluate changes in serum N-glycoproteins and their glycosylation status prior to clinical presentation of pancreatic cancer that may be potential biomarkers. Prediagnosis serum samples pooled according to f...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18122670
更新日期：2017-12-09 00:00:00
abstract：:The coupling of alternative splicing with the nonsense-mediated decay (NMD) pathway maintains quality control of the transcriptome in eukaryotes by eliminating transcripts with premature termination codons (PTC) and fine-tunes gene expression. Long noncoding RNA (lncRNA) can regulate multiple cellular processes, inclu...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21165605
更新日期：2020-08-05 00:00:00
abstract：:The current knowledge about neuroprotective mechanisms in humans after status epilepticus is scarce. One reason is the difficulty to measure possible mediators of these neuroprotective mechanisms. The dawn of microRNA detection in the cerebrospinal fluid (CSF) and the recent advancements in measuring proteins in the C...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms18030490
更新日期：2017-02-24 00:00:00
abstract：:The MP2 and DFT/B3LYP methods at 6-311++G(d,p) and aug-cc-pdz basis sets have been used to probe the origin of relative stability preference for eclipsed acetaldehyde over its bisected counterpart. A relative energy stability range of 1.02 to 1.20 kcal/mol, in favor of the eclipsed conformer, was found and discussed. ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms131115360
更新日期：2012-11-20 00:00:00
abstract：:Proliferation and apoptosis are important physiological processes of preadipocytes. Rev-erbα is a circadian clock gene, and its activity contributes to several physiological processes in various cells. Previous studies demonstrated that Rev-erbα promotes preadipocyte differentiation, but a role of Rev-erbα on preadipo...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20184524
更新日期：2019-09-12 00:00:00
abstract：:Immune modulation is a very modern medical field for targeting viral infections. In the race to develop the best immune modulator against viruses, curcumin, as a natural product, is inexpensive, without side effects, and can stimulate very well certain areas of the human immune system. As a bright yellow component of ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21197150
更新日期：2020-09-28 00:00:00
abstract：:Prenatal smoke exposure (PreSE) is a risk factor for nicotine dependence, which is further enhanced by postnatal smoke exposure (PostSE). One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Higher CYP2A6 activity is...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms22010164
更新日期：2020-12-26 00:00:00
abstract：:Bacillus cereus can survive in the form of spores for prolonged periods posing a serious problem for the manufacture of safe shelf-stable foods of optimal quality. Our study aims at increasing knowledge of B. cereus spores focusing primarily on germination mechanisms to develop novel milder food preservation strategie...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21155198
更新日期：2020-07-22 00:00:00
abstract：:n/a. ...
journal_title：International journal of molecular sciences
pub_type： 评论,杂志文章
doi：10.3390/ijms18050994
更新日期：2017-05-05 00:00:00
abstract：:Circulating tumour cells (CTCs) from liquid biopsies are under current investigation in several cancers, including epithelial ovarian cancer (EOC) but face significant drawbacks in terms of non-standardised methodology, low viable cell numbers and accuracy of CTC identification. In this pilot study, we report that che...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21134813
更新日期：2020-07-07 00:00:00
abstract：:Maize (Zea mays L.) is a host to numerous pathogenic species that impose serious diseases to its ear and foliage, negatively affecting the yield and the quality of the maize crop. A considerable amount of research has been carried out to elucidate mechanisms of maize-pathogen interactions with a major goal to identify...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms161226106
更新日期：2015-11-30 00:00:00
abstract：:The embryos of some angiosperms (usually referred to as chloroembryos) contain chlorophylls during the whole period of embryogenesis. Developing embryos have photochemically active chloroplasts and are able to produce assimilates, further converted in reserve biopolymers, whereas at the late steps of embryogenesis, se...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms18091993
更新日期：2017-09-16 00:00:00
abstract：:This work describes the chemical synthesis, combinatorial selection, and enzymatic evaluation of peptidomimetic fluorescent substrates specific for the trypsin-like (β2) subunit of the 20S human proteasome. After deconvolution of a library comprising nearly 6000 compounds composed of peg substituted diaminopropionic a...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21072396
更新日期：2020-03-31 00:00:00
abstract：:In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucida...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms17060783
更新日期：2016-05-30 00:00:00
abstract：:Kalanchoe brasiliensis and Kalanchoe pinnata are used interchangeably in traditional medicine for treating peptic ulcers and inflammatory problems. In this context, this study aims to characterize the chemical constituents and evaluate the gastroprotective activity of the leaf juices of the two species in acute gastri...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19051265
更新日期：2018-04-24 00:00:00
