2024
Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid
Papini C, Ullah I, Ranjan A, Zhang S, Wu Q, Spasov K, Zhang C, Mothes W, Crawford J, Lindenbach B, Uchil P, Kumar P, Jorgensen W, Anderson K. Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2320713121. PMID: 38621119, PMCID: PMC11046628, DOI: 10.1073/pnas.2320713121.Peer-Reviewed Original ResearchConceptsDirect-acting antiviralsSARS-CoV-2Lack of off-target effectsIn vitro pharmacological profileTreatment of patientsDevelopment of severe symptomsPharmacological propertiesDrug-drug interactionsSARS-CoV-2 infectionProof-of-concept studySARS-CoV-2 M<sup>pro</sup>.Combination regimenImmunocompromised patientsLead compoundsSARS-CoV-2 main proteaseOral doseActive drugTreat infectionsPharmacological profileSARS-CoV-2 MPotential preclinical candidateOff-target effectsPatientsComplete recoveryCapsule formulation
2023
Calreticulin Regulates SARS-CoV-2 Spike Protein Turnover and Modulates SARS-CoV-2 Infectivity
Rahimi N, White M, Amraei R, Lotfollahzadeh S, Xia C, Michalak M, Costello C, Mühlberger E. Calreticulin Regulates SARS-CoV-2 Spike Protein Turnover and Modulates SARS-CoV-2 Infectivity. Cells 2023, 12: 2694. PMID: 38067122, PMCID: PMC10705507, DOI: 10.3390/cells12232694.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectivityCardiovascular complicationsS-RBDSARS-CoV-2 infectionEndothelial cellsMajor clinical hallmarksSpike proteinCOVID-19 patientsCoronavirus disease 2019SARS-CoV-2 spike proteinSARS-CoV-2S proteinProteasomal inhibitor bortezomibHuman endothelial cellsShRNA-mediated knockdownCalcium hemostasisClinical hallmarkDisease 2019Inhibitor bortezomibCalcium homeostasisAcidification of lysosomesRole of calreticulinTreatment of cellsProtein levelsComplicationsDietary amino acids and risk of stroke subtypes: a prospective analysis of 356,000 participants in seven European countries
Tong T, Clarke R, Schmidt J, Huybrechts I, Noor U, Forouhi N, Imamura F, Travis R, Weiderpass E, Aleksandrova K, Dahm C, van der Schouw Y, Overvad K, Kyrø C, Tjønneland A, Kaaks R, Katzke V, Schiborn C, Schulze M, Mayen-Chacon A, Masala G, Sieri S, de Magistris M, Tumino R, Sacerdote C, Boer J, Verschuren W, Brustad M, Nøst T, Crous-Bou M, Petrova D, Amiano P, Huerta J, Moreno-Iribas C, Engström G, Melander O, Johansson K, Lindvall K, Aglago E, Heath A, Butterworth A, Danesh J, Key T. Dietary amino acids and risk of stroke subtypes: a prospective analysis of 356,000 participants in seven European countries. European Journal Of Nutrition 2023, 63: 209-220. PMID: 37804448, PMCID: PMC10799144, DOI: 10.1007/s00394-023-03251-4.Peer-Reviewed Original ResearchConceptsRisk of ischaemic strokeHaemorrhagic strokeRisk of stroke subtypesMultivariable-adjusted Cox regression modelsHazard ratioIschaemic strokeStroke subtypesCountry-specific dietary questionnairesBlood pressureConfidence intervalsEstimate hazard ratiosProline intakeMethodsWe analysed dataMultiple testingStatistically significant associationDietary recallsDietary questionnaireInverse associationCox regression modelsDiastolic blood pressureEPIC studyHigher intakeDietary amino acidsDietary intakeMutual adjustmentMistranslation of the genetic code by a new family of bacterial transfer RNAs
Schuntermann D, Fischer J, Bile J, Gaier S, Shelley B, Awawdeh A, Jahn M, Hoffman K, Westhof E, Söll D, Clarke C, Vargas-Rodriguez O. Mistranslation of the genetic code by a new family of bacterial transfer RNAs. Journal Of Biological Chemistry 2023, 299: 104852. PMID: 37224963, PMCID: PMC10404621, DOI: 10.1016/j.jbc.2023.104852.Peer-Reviewed Original ResearchConceptsTransfer RNAsAmino acidsBacterial transfer RNAsUnfavorable environmental conditionsProlyl-tRNA synthetaseWrong amino acidPoor substrate specificitySubstrate discriminationGrowth defectTransfer RNAGenetic codePosttranslational modificationsProtein reporterTranslation factorsEnvironmental stressFunctional proteinsSubstrate specificityThreonine codonGenetic informationDistinct isoformsPro mutationAntibiotic carbenicillinEscherichia coliNovel familyEnvironmental conditions
2022
Histone H3 proline 16 hydroxylation regulates mammalian gene expression
Liu X, Wang J, Boyer J, Gong W, Zhao S, Xie L, Wu Q, Zhang C, Jain K, Guo Y, Rodriguez J, Li M, Uryu H, Liao C, Hu L, Zhou J, Shi X, Tsai Y, Yan Q, Luo W, Chen X, Strahl B, von Kriegsheim A, Zhang Q, Wang G, Baldwin A, Zhang Q. Histone H3 proline 16 hydroxylation regulates mammalian gene expression. Nature Genetics 2022, 54: 1721-1735. PMID: 36347944, PMCID: PMC9674084, DOI: 10.1038/s41588-022-01212-x.Peer-Reviewed Original ResearchConceptsPost-translational modificationsHistone post-translational modificationsMammalian gene expressionGene expressionHistone H3Mammalian cellsDNA-templated processesTranscriptome-wide analysisTarget gene expressionHydroxylation of prolineWnt/β-cateninChromatin recruitmentHistone codeTarget genesRegulatory marksLysine residuesDirect bindingTriple-negative breast cancerΒ-cateninResidues 16H3ExpressionH3K4me3TrimethylationGenomeA genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy
Ye L, Park JJ, Peng L, Yang Q, Chow RD, Dong MB, Lam SZ, Guo J, Tang E, Zhang Y, Wang G, Dai X, Du Y, Kim HR, Cao H, Errami Y, Clark P, Bersenev A, Montgomery RR, Chen S. A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy. Cell Metabolism 2022, 34: 595-614.e14. PMID: 35276062, PMCID: PMC8986623, DOI: 10.1016/j.cmet.2022.02.009.Peer-Reviewed Original ResearchConceptsCAR T cellsT cell-based immunotherapyRight molecular targetCell-based immunotherapyCAR-T therapyChimeric antigen receptorMultiple cancer modelsCAR-T efficacyFunction CRISPR screensCD8 TPrimary CD8Immune functionImmunological diseasesImmune boosterCancer modelAntigen receptorDistinct gene expressionMolecular targetsCRISPR activation screensMetabolic programsImmunological analysisTherapyCancerEfficacyActivation screens
2019
Contemporary HCV pangenotypic DAA treatment protocols are exclusionary to real world HIV-HCV co-infected patients
Maughan A, Sadigh K, Angulo-Diaz V, Mandimika C, Villanueva M, Lim JK, Ogbuagu O. Contemporary HCV pangenotypic DAA treatment protocols are exclusionary to real world HIV-HCV co-infected patients. BMC Infectious Diseases 2019, 19: 378. PMID: 31053098, PMCID: PMC6500032, DOI: 10.1186/s12879-019-3974-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAminoisobutyric AcidsAnti-Retroviral AgentsAntiviral AgentsBenzimidazolesCarbamatesCoinfectionCyclopropanesDrug InteractionsFemaleHepacivirusHepatitis CHeterocyclic Compounds, 4 or More RingsHIV InfectionsHumansLactams, MacrocyclicLeucineLiver CirrhosisMaleMiddle AgedProlinePyrrolidinesQuinoxalinesSofosbuvirSulfonamidesTreatment OutcomeViral LoadConceptsHIV-HCVExclusion criteriaClinical trialsHIV-HCV co-infected patientsNew hepatitis C treatmentsHepatitis C virus infectionCo-infected patientsHIV patient populationC virus infectionGlecaprevir/pibrentasvirSofosbuvir/velpatasvirExcellent cure ratesHIV viral loadMajority of patientsHepatitis C treatmentInjection drug useReal-world populationART regimenHCV agentsCurrent regimensDecompensated cirrhosisViral loadPangenotypic activityCure ratePatient population
2018
cis‐Proline mutants of quiescin sulfhydryl oxidase 1 with altered redox properties undermine extracellular matrix integrity and cell adhesion in fibroblast cultures
Javitt G, Grossman‐Haham I, Alon A, Resnick E, Mutsafi Y, Ilani T, Fass D. cis‐Proline mutants of quiescin sulfhydryl oxidase 1 with altered redox properties undermine extracellular matrix integrity and cell adhesion in fibroblast cultures. Protein Science 2018, 28: 228-238. PMID: 30367560, PMCID: PMC6295897, DOI: 10.1002/pro.3537.Peer-Reviewed Original ResearchConceptsQuiescin sulfhydryl oxidase 1Protein disulfide isomeraseSulfhydryl oxidase 1Thioredoxin superfamilyCatalyst of disulfide bond formationDisulfide isomeraseCis-prolineProtein disulfide isomerase familyEffects of such mutationsThioredoxin-fold proteinsCell adhesionAmino acidsEffects of mutationsExtracellular matrix assemblyCanonical amino acidsActive-site regionDisulfide bond formationRedox-active enzymesSuperfamily enzymesSequence homologyFibroblast culturesBacterial enzymesMutated residuesMutantsDistant member
2017
Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus
Karimy JK, Zhang J, Kurland DB, Theriault BC, Duran D, Stokum JA, Furey CG, Zhou X, Mansuri MS, Montejo J, Vera A, DiLuna ML, Delpire E, Alper SL, Gunel M, Gerzanich V, Medzhitov R, Simard JM, Kahle KT. Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus. Nature Medicine 2017, 23: 997-1003. PMID: 28692063, DOI: 10.1038/nm.4361.Peer-Reviewed Original ResearchMeSH KeywordsAcetazolamideAnimalsAntioxidantsBlotting, WesternBumetanideCerebral HemorrhageCerebral VentriclesCerebrospinal FluidChoroid PlexusDiureticsGene Knockdown TechniquesGene Knockout TechniquesHydrocephalusImmunoblottingImmunohistochemistryImmunoprecipitationInflammationNF-kappa BProlineProtein Serine-Threonine KinasesRatsRats, WistarSalicylanilidesSolute Carrier Family 12, Member 2SulfonamidesThiocarbamatesToll-Like Receptor 4Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia: a double-blind, placebo-controlled, randomised withdrawal phase 2a trial
Zakrzewska JM, Palmer J, Morisset V, Giblin GM, Obermann M, Ettlin DA, Cruccu G, Bendtsen L, Estacion M, Derjean D, Waxman SG, Layton G, Gunn K, Tate S, investigators S. Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia: a double-blind, placebo-controlled, randomised withdrawal phase 2a trial. The Lancet Neurology 2017, 16: 291-300. PMID: 28216232, DOI: 10.1016/s1474-4422(17)30005-4.Peer-Reviewed Original ResearchConceptsDouble-blind phaseFrequent adverse eventsOpen-label phaseSerious adverse eventsPhase 2a trialAdverse eventsTrigeminal neuralgiaSodium channel blockersTreatment failurePrimary endpointInteractive web response systemSelective sodium channel blockerPhase 2a studyCommon adverse eventsDouble-blind treatmentOpen-label treatmentSecondary care centresWeb response systemPhase 1 studyFuture clinical trialsSimilar adverse eventsNumber of patientsSodium channel blockers carbamazepineComputer-generated scheduleEligible patients
2016
Severe Elevation of Liver Enzymes Does Not Necessarily Require Treatment Interruption in Patients Treated With a Combination of Paritaprevir/Ritonavir/Ombitasvir Plus Dasabuvir for HCV Infection
Saadi T, Khoury J. Severe Elevation of Liver Enzymes Does Not Necessarily Require Treatment Interruption in Patients Treated With a Combination of Paritaprevir/Ritonavir/Ombitasvir Plus Dasabuvir for HCV Infection. Journal Of Clinical Gastroenterology 2016, 50: 799. PMID: 27380458, DOI: 10.1097/mcg.0000000000000587.Commentaries, Editorials and LettersMeSH Keywords2-NaphthylamineAlanine TransaminaseAnilidesAntiviral AgentsAspartate AminotransferasesCarbamatesCyclopropanesDrug Therapy, CombinationFemaleHepatitis C, ChronicHumansLactams, MacrocyclicMacrocyclic CompoundsMiddle AgedProlineRibavirinRitonavirSulfonamidesUracilValineWithholding TreatmentHelix perturbations in membrane proteins assist in inter-helical interactions and optimal helix positioning in the bilayer
Shelar A, Bansal M. Helix perturbations in membrane proteins assist in inter-helical interactions and optimal helix positioning in the bilayer. Biochimica Et Biophysica Acta 2016, 1858: 2804-2817. PMID: 27521749, DOI: 10.1016/j.bbamem.2016.08.003.Peer-Reviewed Original ResearchConceptsInter-helical interactionsMembrane proteinsTM regionHelix perturbationTM helicesΠ-helixDistinct sequence signaturesIntegral membrane proteinsLow sequence identityHeme-copper oxidasesTransmembrane helicesProtein functionSequence signaturesSequence identityHydrophobic mismatchΑ-helixProtein chainsAmino acidsHelical fragmentsCopper oxidasesProteinHelix terminiHelixTerminusBilayers
2014
Virologic response and haematologic toxicity of boceprevir‐ and telaprevir‐containing regimens in actual clinical settings
Butt AA, Yan P, Shaikh OS, Freiberg MS, Re V, Justice AC, Sherman KE, Team T. Virologic response and haematologic toxicity of boceprevir‐ and telaprevir‐containing regimens in actual clinical settings. Journal Of Viral Hepatitis 2014, 22: 691-700. PMID: 25524834, PMCID: PMC5020421, DOI: 10.1111/jvh.12375.Peer-Reviewed Original ResearchConceptsSustained virologic responsePEG/RBVHaematologic toxicityActual clinical settingsSVR ratesVirologic responseClinical settingHaematologic adverse eventsHCV Infected VeteransInterferon/ribavirinHCV genotype 1HCV RNA valuesPivotal clinical trialsHepatitis C virusBaseline cirrhosisHIV coinfectionPrimary endpointTreatment-naïveAdverse eventsC virusClinical trialsGenotype 1Genotype 1aSevere toxicityBoceprevirManagement of treatment‐naïve chronic hepatitis C genotype 1 patients: a cost‐effectiveness analysis of treatment options
Cortesi PA, Ciaccio A, Rota M, Lim JK, De Salvia S, Okolicsanyi S, Vinci M, Belli LS, Mantovani LG, Strazzabosco M. Management of treatment‐naïve chronic hepatitis C genotype 1 patients: a cost‐effectiveness analysis of treatment options. Journal Of Viral Hepatitis 2014, 22: 175-183. PMID: 25040391, DOI: 10.1111/jvh.12278.Peer-Reviewed Original ResearchConceptsIncremental cost-effectiveness ratioEnd-stage liver diseaseCost-effectiveness analysisF3-F4Liver diseaseChronic hepatitis C genotype 1 patientsHepatitis C genotype 1 patientsItalian National Health System perspectiveNational Health System perspectiveResponse-guided therapyGenotype 1 patientsMETAVIR fibrosis stageHealth system perspectiveQuality-adjusted life yearsPatient selection strategiesCost-effectiveness ratioG1 patientsNaive patientsTriple therapyOnly patientsAdvanced fibrosisFuture regimensMore regimensTreatment optionsFibrosis stageControl of a Salmonella virulence operon by proline-charged tRNAPro
Lee EJ, Choi J, Groisman EA. Control of a Salmonella virulence operon by proline-charged tRNAPro. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 3140-3145. PMID: 24516160, PMCID: PMC3939920, DOI: 10.1073/pnas.1316209111.Peer-Reviewed Original Research5' Untranslated RegionsAmino Acid SequenceAnimalsBacterial ProteinsBase PairingBase SequenceCation Transport ProteinsCodonGene Expression Regulation, BacterialHost-Pathogen InteractionsMiceMolecular Sequence DataOligodeoxyribonucleotidesOpen Reading FramesProlineReal-Time Polymerase Chain ReactionRNA, Transfer, ProSalmonella typhimuriumVirulence
2012
New Pharmacotherapy for Hepatitis C
Assis DN, Lim JK. New Pharmacotherapy for Hepatitis C. Clinical Pharmacology & Therapeutics 2012, 92: 294-305. PMID: 22850602, DOI: 10.1038/clpt.2012.103.Peer-Reviewed Original ResearchConceptsHepatitis CChronic hepatitis C infectionMajor global public health burdenGlobal public health burdenViral eradication ratesHepatitis C infectionProtease inhibitors boceprevirPublic health burdenDrug Administration approvalHepatitis C virus proteaseHCV pharmacotherapyC infectionEradication rateViral eradicationImproved tolerabilitySubstantial morbidityAntiviral therapyAdministration approvalNew pharmacotherapiesHealth burdenSuperior efficacyAntiviral agentsUS FoodPharmacotherapyShort durationInteraction of the Histone mRNA Hairpin with Stem–Loop Binding Protein (SLBP) and Regulation of the SLBP–RNA Complex by Phosphorylation and Proline Isomerization
Zhang M, Lam TT, Tonelli M, Marzluff WF, Thapar R. Interaction of the Histone mRNA Hairpin with Stem–Loop Binding Protein (SLBP) and Regulation of the SLBP–RNA Complex by Phosphorylation and Proline Isomerization. Biochemistry 2012, 51: 3215-3231. PMID: 22439849, PMCID: PMC3328597, DOI: 10.1021/bi2018255.Peer-Reviewed Original ResearchConceptsStem-loop binding proteinStem-loop structureHistone mRNAProline isomerizationThreonine phosphorylationEnd formationC base pairsReplication-dependent histone mRNAsBase pairsBinding proteinPossible structural roleAdjacent prolineHistone proteinsRibonucleoprotein complexesHelix motifMRNA hairpinsMRNA complexesUntranslated regionStructural roleFirst binding sitePhosphorylationProteinComplex dissociationCritical hingeMRNA
2011
The RabGAP Proteins Gyp5p and Gyl1p Recruit the BAR Domain Protein Rvs167p for Polarized Exocytosis
Prigent M, Boy‐Marcotte E, Chesneau L, Gibson K, Dupré‐Crochet S, Tisserand H, Verbavatz J, Cuif M. The RabGAP Proteins Gyp5p and Gyl1p Recruit the BAR Domain Protein Rvs167p for Polarized Exocytosis. Traffic 2011, 12: 1084-1097. PMID: 21554509, DOI: 10.1111/j.1600-0854.2011.01218.x.Peer-Reviewed Original ResearchMeSH KeywordsExocytosisGlucan Endo-1,3-beta-D-GlucosidaseGTPase-Activating ProteinsMicrofilament ProteinsMutationNerve Tissue ProteinsProlineProtein BindingProtein Interaction Domains and Motifsrab GTP-Binding ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSecretory Vesiclessrc Homology Domains
2010
A Bacterial mRNA Leader that Employs Different Mechanisms to Sense Disparate Intracellular Signals
Park SY, Cromie MJ, Lee EJ, Groisman EA. A Bacterial mRNA Leader that Employs Different Mechanisms to Sense Disparate Intracellular Signals. Cell 2010, 142: 737-748. PMID: 20813261, PMCID: PMC2967377, DOI: 10.1016/j.cell.2010.07.046.Peer-Reviewed Original ResearchMeSH Keywords5' Untranslated RegionsAdenosine TriphosphatasesBacterial ProteinsBase SequenceGene Expression Regulation, BacterialMagnesiumMembrane Transport ProteinsMolecular Sequence DataProlineRegulatory Sequences, Ribonucleic AcidRNA, MessengerSalmonella typhimuriumSequence AlignmentTranscription, GeneticConceptsLeader sequenceExploiting a Global Regulator for Small Molecule Discovery in Photorhabdus luminescens
Kontnik R, Crawford JM, Clardy J. Exploiting a Global Regulator for Small Molecule Discovery in Photorhabdus luminescens. ACS Chemical Biology 2010, 5: 659-665. PMID: 20524642, PMCID: PMC2912427, DOI: 10.1021/cb100117k.Peer-Reviewed Original ResearchConceptsGlobal transcriptional regulatorSmall moleculesSecondary metabolite productionGenes/lociTight regulatory controlUseful biological probesSmall molecule discoverySuch small moleculesGlobal regulatorBacterial genomesFunctional diversityInsect larvaeTranscriptional regulatorsTranscriptional repressorComplex symbiosisNematode wormsMetabolite productionMolecule discoveryPhotorhabdusMutantsDramatic upregulationSymbiosisRegulatory controlRemarkable rangeRegulator
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply