J Chem Inf Model - Molecular dynamics simulations reveal a novel mechanism for ATP inhibition of insulin degrading enzyme.

Tópicos

{ gene(2352) biolog(1181) express(1162) }
{ bind(1733) structur(1185) ligand(1036) }
{ import(1318) role(1303) understand(862) }
{ compound(1573) activ(1297) structur(1058) }
{ sampl(1606) size(1419) use(1276) }
{ activ(1452) weight(1219) physic(1104) }
{ imag(1947) propos(1133) code(1026) }
{ system(1976) rule(880) can(841) }
{ motion(1329) object(1292) video(1091) }
{ perform(1367) use(1326) method(1137) }
{ activ(1138) subject(705) human(624) }
{ model(3404) distribut(989) bayesian(671) }
{ imag(2675) segment(2577) method(1081) }
{ patient(2315) diseas(1263) diabet(1191) }
{ take(945) account(800) differ(722) }
{ treatment(1704) effect(941) patient(846) }
{ chang(1828) time(1643) increas(1301) }
{ method(1557) propos(1049) approach(1037) }
{ control(1307) perform(991) simul(935) }
{ model(2220) cell(1177) simul(1124) }
{ data(3963) clinic(1234) research(1004) }
{ studi(1410) differ(1259) use(1210) }
{ model(2341) predict(2261) use(1141) }
{ studi(1119) effect(1106) posit(819) }
{ time(1939) patient(1703) rate(768) }
{ can(981) present(881) function(850) }
{ analysi(2126) use(1163) compon(1037) }
{ use(976) code(926) identifi(902) }
{ result(1111) use(1088) new(759) }
{ estim(2440) model(1874) function(577) }
{ can(774) often(719) complex(702) }
{ data(1737) use(1416) pattern(1282) }
{ inform(2794) health(2639) internet(1427) }
{ measur(2081) correl(1212) valu(896) }
{ imag(1057) registr(996) error(939) }
{ sequenc(1873) structur(1644) protein(1328) }
{ method(1219) similar(1157) match(930) }
{ featur(3375) classif(2383) classifi(1994) }
{ imag(2830) propos(1344) filter(1198) }
{ network(2748) neural(1063) input(814) }
{ studi(2440) review(1878) systemat(933) }
{ assess(1506) score(1403) qualiti(1306) }
{ surgeri(1148) surgic(1085) robot(1054) }
{ framework(1458) process(801) describ(734) }
{ problem(2511) optim(1539) algorithm(950) }
{ error(1145) method(1030) estim(1020) }
{ learn(2355) train(1041) set(1003) }
{ concept(1167) ontolog(924) domain(897) }
{ clinic(1479) use(1117) guidelin(835) }
{ algorithm(1844) comput(1787) effici(935) }
{ extract(1171) text(1153) clinic(932) }
{ data(1714) softwar(1251) tool(1186) }
{ design(1359) user(1324) use(1319) }
{ care(1570) inform(1187) nurs(1089) }
{ general(901) number(790) one(736) }
{ method(984) reconstruct(947) comput(926) }
{ search(2224) databas(1162) retriev(909) }
{ featur(1941) imag(1645) propos(1176) }
{ case(1353) use(1143) diagnosi(1136) }
{ howev(809) still(633) remain(590) }
{ risk(3053) factor(974) diseas(938) }
{ perform(999) metric(946) measur(919) }
{ research(1085) discuss(1038) issu(1018) }
{ system(1050) medic(1026) inform(1018) }
{ visual(1396) interact(850) tool(830) }
{ blood(1257) pressur(1144) flow(957) }
{ spatial(1525) area(1432) region(1030) }
{ record(1888) medic(1808) patient(1693) }
{ health(3367) inform(1360) care(1135) }
{ model(3480) simul(1196) paramet(876) }
{ monitor(1329) mobil(1314) devic(1160) }
{ ehr(2073) health(1662) electron(1139) }
{ state(1844) use(1261) util(961) }
{ research(1218) medic(880) student(794) }
{ patient(2837) hospit(1953) medic(668) }
{ model(2656) set(1616) predict(1553) }
{ data(2317) use(1299) case(1017) }
{ age(1611) year(1155) adult(843) }
{ medic(1828) order(1363) alert(1069) }
{ signal(2180) analysi(812) frequenc(800) }
{ cost(1906) reduc(1198) effect(832) }
{ group(2977) signific(1463) compar(1072) }
{ data(3008) multipl(1320) sourc(1022) }
{ first(2504) two(1366) second(1323) }
{ intervent(3218) particip(2042) group(1664) }
{ patient(1821) servic(1111) care(1106) }
{ use(2086) technolog(871) perceiv(783) }
{ health(1844) social(1437) communiti(874) }
{ structur(1116) can(940) graph(676) }
{ high(1669) rate(1365) level(1280) }
{ cancer(2502) breast(956) screen(824) }
{ use(1733) differ(960) four(931) }
{ drug(1928) target(777) effect(648) }
{ implement(1333) system(1263) develop(1122) }
{ survey(1388) particip(1329) question(1065) }
{ decis(3086) make(1611) patient(1517) }
{ process(1125) use(805) approach(778) }
{ method(1969) cluster(1462) data(1082) }
{ method(2212) result(1239) propos(1039) }
{ detect(2391) sensit(1101) algorithm(908) }

Resumo

Regulation of brain levels of the Amyloid-? 42 (A?42) polypeptide by IDE has recently been linked with possible routes for new therapies against Alzheimer's disease (AD). One important aspect is the regulatory mechanism of IDE by ATP, which is an IDE activator in degrading small peptides and an inhibitor in degrading larger peptides, such as A?42. This relationship was investigated in this study. We present molecular dynamics simulations of A?42 complexed with IDE, in the absence or presence of either ATP or excess Na(+) and Cl(-) ions. Results suggest a previously unreported inhibition mechanism that depends on charge-induced structural modifications in the active site and interactions simultaneously involving ATP, A?42, and IDE. Such interactions exist only when both ATP and A?42 are simultaneously present in the catalytic chamber. This mechanism results in allosteric, noncompetitive inhibition with apparent decrease of substrate affinity, in accordance with experiment.

Resumo Limpo

regul brain level amyloid polypeptid ide recent link possibl rout new therapi alzheim diseas ad one import aspect regulatori mechan ide atp ide activ degrad small peptid inhibitor degrad larger peptid relationship investig studi present molecular dynam simul complex ide absenc presenc either atp excess na cl ion result suggest previous unreport inhibit mechan depend chargeinduc structur modif activ site interact simultan involv atp ide interact exist atp simultan present catalyt chamber mechan result alloster noncompetit inhibit appar decreas substrat affin accord experi

Resumos Similares

Wiley Interdiscip Rev Syst Biol Med - The adaptor protein LAT serves as an integration node for signaling pathways that drive T cell activation. ( 0,838822946053193 )
Wiley Interdiscip Rev Syst Biol Med - ?-Arrestin-kinase scaffolds: turn them on or turn them off? ( 0,827144735237464 )
Wiley Interdiscip Rev Syst Biol Med - Protein microarrays for genome-wide posttranslational modification analysis. ( 0,815508257062904 )
J Chem Inf Model - Discovery of a novel selective PPAR ligand with partial agonist binding properties by integrated in silico/in vitro work flow. ( 0,788277087256664 )
Wiley Interdiscip Rev Syst Biol Med - miRNA regulation in the context of functional protein networks: principles and applications. ( 0,785762243176415 )
J. Comput. Biol. - Chromatin properties of regulatory DNA probed by manipulation of transcription factors. ( 0,767909574459775 )
Comput Biol Chem - Computational analysis of 3'UTR region of CASP3 with respect to miRSNPs and SNPs in targetting miRNAs. ( 0,767214449696062 )
Comput. Biol. Med. - Genome-wide identification and structure-function studies of proteases and protease inhibitors in Cicer arietinum (chickpea). ( 0,766071592934185 )
J Chem Inf Model - Scoring function based approach for locating binding sites and understanding recognition mechanism of protein-DNA complexes. ( 0,760899442805402 )
Brief. Bioinformatics - Identifying miRNAs, targets and functions. ( 0,759579703498488 )
J. Comput. Biol. - Informational requirements for transcriptional regulation. ( 0,758902112326768 )
Wiley Interdiscip Rev Syst Biol Med - Noncoding RNAs in gene regulation. ( 0,756861796502852 )
Comput. Biol. Med. - A molecular prospective provides new insights into implication of PDYN and OPRK1 genes in alcohol dependence. ( 0,755520943970945 )
Wiley Interdiscip Rev Syst Biol Med - Bioimage informatics for understanding spatiotemporal dynamics of cellular processes. ( 0,753501542693788 )
Wiley Interdiscip Rev Syst Biol Med - Diverse functional networks of Tbx3 in development and disease. ( 0,748121721795429 )
Comput. Biol. Med. - Mathematical modeling and sensitivity analysis of the integrated TNFa-mediated apoptotic pathway for identifying key regulators. ( 0,74583533022836 )
J Integr Bioinform - Computer and statistical analysis of transcription factor binding and chromatin modifications by ChIP-seq data in embryonic stem cell. ( 0,74368576168794 )
Comput Math Methods Med - Identification and functional annotation of genome-wide ER-regulated genes in breast cancer based on ChIP-Seq data. ( 0,740193528297188 )
Comput Math Methods Med - Integrating gene expression and protein interaction data for signaling pathway prediction of Alzheimer's disease. ( 0,739767244048675 )
Wiley Interdiscip Rev Syst Biol Med - Stem cell bioengineering at the interface of systems-based models and high-throughput platforms. ( 0,736426281569084 )
J Chem Inf Model - Ligand binding and functional selectivity of L-tryptophan metabolites at the mouse aryl hydrocarbon receptor (mAhR). ( 0,734299691774718 )
Comput Biol Chem - Detecting adaptive evolution and functional divergence in aminocyclopropane-1-carboxylate synthase (ACS) gene family. ( 0,72979755177616 )
Comput Biol Chem - Identification of novel splice variants and exons of human endothelial cell-specific chemotaxic regulator (ECSCR) by bioinformatics analysis. ( 0,72853076799145 )
Brief. Bioinformatics - Apoptosis regulatory protein-protein interaction demonstrates hierarchical scale-free fractal network. ( 0,728310880793033 )
Med Biol Eng Comput - Cell sheet integrity and nanomechanical breakdown during programmed cell death. ( 0,727649981581631 )
J. Comput. Biol. - An algorithm for efficient identification of branched metabolic pathways. ( 0,726258866355018 )
Wiley Interdiscip Rev Syst Biol Med - Establishing the stem cell state: insights from regulatory network analysis of blood stem cell development. ( 0,725771097693035 )
J Biomed Inform - Inferring cell cycle feedback regulation from gene expression data. ( 0,724557958240046 )
Comput Math Methods Med - Understanding the pathogenesis of Kawasaki disease by network and pathway analysis. ( 0,722540952077011 )
Comput Biol Chem - Mutually exclusive binding of APPL(PH) to BAR domain and Reptin regulates ?-catenin dependent transcriptional events. ( 0,71914809394716 )
J Integr Bioinform - Predicting breast cancer chemotherapeutic response using a novel tool for microarray data analysis. ( 0,715372657698314 )
AMIA Annu Symp Proc - Towards mechanism classifiers: expression-anchored Gene Ontology signature predicts clinical outcome in lung adenocarcinoma patients. ( 0,715366096531581 )
J Integr Bioinform - A study of the short and long-term regulation of E. coli metabolic pathways. ( 0,713970568523345 )
Wiley Interdiscip Rev Syst Biol Med - Using variability in gene expression as a tool for studying gene regulation. ( 0,71356238039728 )
J Integr Bioinform - Assembling cell context-specific gene sets: a case in cardiomyopathy. ( 0,711043097562751 )
Wiley Interdiscip Rev Syst Biol Med - Systems biology of adipose tissue metabolism: regulation of growth, signaling and inflammation. ( 0,710976173187433 )
J. Comput. Biol. - Bioinformatics method to analyze the mechanism of pancreatic cancer disorder. ( 0,710862875358952 )
J Biomed Inform - A comparative study of covariance selection models for the inference of gene regulatory networks. ( 0,709922371362164 )
J Am Med Inform Assoc - Extracting coordinated patterns of DNA methylation and gene expression in ovarian cancer. ( 0,708124248945823 )
Artif Intell Med - An extensive analysis of disease-gene associations using network integration and fast kernel-based gene prioritization methods. ( 0,707150099759152 )
Comput Biol Chem - Expression patterns of photoperiod and temperature regulated heading date genes in Oryza sativa. ( 0,706104846162309 )
Wiley Interdiscip Rev Syst Biol Med - Genome-wide approaches in the study of microRNA biology. ( 0,705025259256164 )
Comput. Biol. Med. - Cellular oncomiR orthologue in EBV oncogenesis. ( 0,704381817256626 )
J Am Med Inform Assoc - Network models of genome-wide association studies uncover the topological centrality of protein interactions in complex diseases. ( 0,704089130838421 )
J Biomed Inform - Gene pathways and subnetworks distinguish between major glioma subtypes and elucidate potential underlying biology. ( 0,703919270841601 )
Comput Math Methods Med - First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. ( 0,703594609750277 )
Comput. Biol. Med. - Interplay between Fur and HNS in controlling virulence gene expression in Salmonella typhimurium. ( 0,702524363304822 )
Wiley Interdiscip Rev Syst Biol Med - Recent advances in prostate development and links to prostatic diseases. ( 0,702298758173509 )
Wiley Interdiscip Rev Syst Biol Med - Network biology: a direct approach to study biological function. ( 0,700676620351245 )
Comput Biol Chem - Using gene expression programming to infer gene regulatory networks from time-series data. ( 0,700095832880791 )
J Biomed Inform - Prioritization of potential candidate disease genes by topological similarity of protein-protein interaction network and phenotype data. ( 0,700091076035555 )
J Biomed Inform - Data driven linear algebraic methods for analysis of molecular pathways: application to disease progression in shock/trauma. ( 0,700083657195212 )
J Am Med Inform Assoc - An integrated approach to identify causal network modules of complex diseases with application to colorectal cancer. ( 0,699851926996714 )
Comput. Biol. Med. - Identification and analysis of the regulatory network of Myc and microRNAs from high-throughput experimental data. ( 0,699813152962667 )
Artif Intell Med - Identifying regulatory relationships among genomic loci, biological pathways, and disease. ( 0,698313895001485 )
Comput. Biol. Med. - Predicting miRNA-mediated gene silencing mode based on miRNA-target duplex features. ( 0,698111161715683 )
Comput Biol Chem - Prediction and verification of microRNAs related to proline accumulation under drought stress in potato. ( 0,695965717556947 )
J Integr Bioinform - An integrative bioinformatics framework for genome-scale multiple level network reconstruction of rice. ( 0,695708749377959 )
Sci Data - DNA methylation temporal profiling following peripheral versus central nervous system axotomy. ( 0,69481637676564 )
Comput Math Methods Med - Dynamic regulatory network reconstruction for Alzheimer's disease based on matrix decomposition techniques. ( 0,693891803665777 )
J Integr Bioinform - Network expansion and pathway enrichment analysis towards biologically significant findings from microarrays. ( 0,693440128954894 )
Brief. Bioinformatics - Towards a comprehensive picture of the genetic landscape of complex traits. ( 0,692985889435044 )
Wiley Interdiscip Rev Syst Biol Med - Integrating omics into the cardiac differentiation of human pluripotent stem cells. ( 0,691552905361302 )
Comput Biol Chem - Disruption of murine Tcte3-3 induces tissue specific apoptosis via co-expression of Anxa5 and Pebp1. ( 0,691131037560029 )
J Am Med Inform Assoc - Complex-disease networks of trait-associated single-nucleotide polymorphisms (SNPs) unveiled by information theory. ( 0,691050204532227 )
Comput. Biol. Med. - Network-based approach reveals Y chromosome influences prostate cancer susceptibility. ( 0,691026817170252 )
Wiley Interdiscip Rev Syst Biol Med - Regulatory variation: an emerging vantage point for cancer biology. ( 0,690947420227353 )
J Am Med Inform Assoc - Identifying disease genes and module biomarkers by differential interactions. ( 0,690493162712371 )
Brief. Bioinformatics - Revealing the architecture of genetic and epigenetic regulation: a maximum likelihood model. ( 0,690321665297079 )
J Chem Inf Model - Unbinding pathways of GW4064 from human farnesoid X receptor as revealed by molecular dynamics simulations. ( 0,68942049395457 )
J Biomed Inform - The detection of risk pathways, regulated by miRNAs, via the integration of sample-matched miRNA-mRNA profiles and pathway structure. ( 0,688920154126898 )
Brief. Bioinformatics - Exploring the function of genetic variants in the non-coding genomic regions: approaches for identifying human regulatory variants affecting gene expression. ( 0,688172159488259 )
Comput. Biol. Med. - Revealing pathway maps of renal cell carcinoma by gene expression change. ( 0,687724547408681 )
Wiley Interdiscip Rev Syst Biol Med - Sex and the circuitry: progress toward a systems-level understanding of vertebrate sex determination. ( 0,687120637443842 )
Comput Math Methods Med - Systematic analysis of time-series gene expression data on tumor cell-selective apoptotic responses to HDAC inhibitors. ( 0,68635657247302 )
J Biomed Inform - miRWalk--database: prediction of possible miRNA binding sites by walking the genes of three genomes. ( 0,68600431424485 )
Comput Biol Chem - Exploring the complexity of pathway-drug relationships using latent Dirichlet allocation. ( 0,684544004641022 )
Comput Biol Chem - GPEC: a Cytoscape plug-in for random walk-based gene prioritization and biomedical evidence collection. ( 0,684347123275253 )
Comput Biol Chem - In silico analysis of cis-acting regulatory elements in 5' regulatory regions of sucrose transporter gene families in rice (Oryza sativa Japonica) and Arabidopsis thaliana. ( 0,684217534551025 )
Comput. Biol. Med. - A review on the computational approaches for gene regulatory network construction. ( 0,682576480307441 )
Artif Intell Med - Self-focusing therapeutic gene delivery with intelligent gene vector swarms: intra-swarm signalling through receptor transgene expression in targeted cells. ( 0,680612176871417 )
Comput. Biol. Med. - Degrees of separation as a statistical tool for evaluating candidate genes. ( 0,680437461419083 )
Wiley Interdiscip Rev Syst Biol Med - Postgenomic technologies targeting the Wnt signaling network. ( 0,678260546787263 )
J. Comput. Biol. - Stochastic simulation of notch signaling reveals novel factors that mediate the differentiation of neural stem cells. ( 0,677740702619718 )
Brief. Bioinformatics - Identification of aberrant pathways and network activities from high-throughput data. ( 0,677620194396857 )
J. Comput. Biol. - A stationary wavelet entropy-based clustering approach accurately predicts gene expression. ( 0,677024838424186 )
Wiley Interdiscip Rev Syst Biol Med - Reverse-engineering human regulatory networks. ( 0,676635923627537 )
Wiley Interdiscip Rev Syst Biol Med - Where gene discovery turns into systems biology: genome-scale RNAi screens in Drosophila. ( 0,675993541117157 )
J. Comput. Biol. - A topology-based score for pathway enrichment. ( 0,675681731176804 )
Comput Biol Chem - A computational method of predicting regulatory interactions in Arabidopsis based on gene expression data and sequence information. ( 0,675619756006514 )
J. Comput. Biol. - Vavien: an algorithm for prioritizing candidate disease genes based on topological similarity of proteins in interaction networks. ( 0,675061845122163 )
J Biomed Inform - Systems-based biological concordance and predictive reproducibility of gene set discovery methods in cardiovascular disease. ( 0,674758360305085 )
J Biomed Inform - Independent component analysis: mining microarray data for fundamental human gene expression modules. ( 0,674663248540881 )
Comput Biol Chem - Gene expression patterns combined with bioinformatics analysis identify genes associated with cholangiocarcinoma. ( 0,671233747889496 )
Wiley Interdiscip Rev Syst Biol Med - Signaling networks in palate development. ( 0,67076433177082 )
Methods Inf Med - Pathway based microarray analysis, utilising enzyme compounds and cascade events. ( 0,6702544276946 )
Comput Biol Chem - Identification of all trinucleotide circular codes. ( 0,669869196773213 )
Wiley Interdiscip Rev Syst Biol Med - Understanding multimodal biological decisions from single cell and population dynamics. ( 0,669869196773213 )
Comput Biol Chem - lncRNAMap: a map of putative regulatory functions in the long non-coding transcriptome. ( 0,669689504025294 )
Comput Biol Chem - Revealing weak differential gene expressions and their reproducible functions associated with breast cancer metastasis. ( 0,669332549971252 )