2021
Reengineering protein-phosphorylation switches
Kholodenko B, Okada M. Reengineering protein-phosphorylation switches. Science 2021, 373: 25-26. PMID: 34210865, PMCID: PMC8327301, DOI: 10.1126/science.abj5028.Peer-Reviewed Original Research
2020
Systems biology approaches to macromolecules: the role of dynamic protein assemblies in information processing
Rukhlenko O, Kholodenko B, Kolch W. Systems biology approaches to macromolecules: the role of dynamic protein assemblies in information processing. Current Opinion In Structural Biology 2020, 67: 61-68. PMID: 33126139, PMCID: PMC8062579, DOI: 10.1016/j.sbi.2020.09.007.Peer-Reviewed Original ResearchConceptsProtein assembliesProtein complex dynamicsDynamic protein assembliesMacromolecular protein assembliesSignal transduction networksSystems biology approachMEK-ERK pathwayProtein complexesTransduction networksCellular processesBiology approachMolecular machinesRAS-RAFOncogenic mutationsStructural studiesDrug resistanceTemporal dynamicsAssemblyRecent progressTumorigenesisMutationsPicture highlightsFine tuningPathwayDynamic process
2019
Mapping connections in signaling networks with ambiguous modularity
Lill D, Rukhlenko O, Mc Elwee A, Kashdan E, Timmer J, Kholodenko B. Mapping connections in signaling networks with ambiguous modularity. Npj Systems Biology And Applications 2019, 5: 19. PMID: 31149348, PMCID: PMC6533310, DOI: 10.1038/s41540-019-0096-1.Peer-Reviewed Original ResearchConceptsModular Response AnalysisProtein abundanceProtein complexesNetwork reconstructionDownstream modulesRetroactive interactionsUpstream moduleComputational restorationNetwork modulesSuite of methodsAbundanceSuch complexesExperimental approachComplexesProteinEnzymePathwaySequestration effectNetwork responseDifferent modules
2018
Reconstructing static and dynamic models of signaling pathways using Modular Response Analysis
Santra T, Rukhlenko O, Zhernovkov V, Kholodenko B. Reconstructing static and dynamic models of signaling pathways using Modular Response Analysis. Current Opinion In Systems Biology 2018, 9: 11-21. DOI: 10.1016/j.coisb.2018.02.003.Peer-Reviewed Original ResearchModular Response AnalysisNetwork reconstruction methodsPhysics-based methodBiochemical pathwaysBiological networksNetwork reconstructionTopological modelDynamic modelResponse analysisNetwork modulesCertain conditionsPathwayReconstruction methodMechanistic modelEntire networkModelCore theoryReformulationPerturbationsTheorySufficient numberNetworkGlobal responseDirection
2015
Phosphorylation of RAF Kinase Dimers Drives Conformational Changes that Facilitate Transactivation
Jambrina P, Rauch N, Pilkington R, Rybakova K, Nguyen L, Kholodenko B, Buchete N, Kolch W, Rosta E. Phosphorylation of RAF Kinase Dimers Drives Conformational Changes that Facilitate Transactivation. Angewandte Chemie 2015, 128: 995-998. DOI: 10.1002/ange.201509272.Peer-Reviewed Original ResearchRAF dimerizationStructure-based mechanismPhysiological activation mechanismKinase dimerΑC-helixAcidic motifRaf kinaseRAF dimersR-spineConformational changesTrp residuesRAF inhibitorsPhosphorylationActivation mechanismKey playersSalt bridgeMotifKinaseCooperative interactionsRafPersonalized cancer therapyActive siteImportant targetResiduesPathway
2000
Diffusion control of protein phosphorylation in signal transduction pathways
KHOLODENKO B, BROWN G, HOEK J. Diffusion control of protein phosphorylation in signal transduction pathways. Biochemical Journal 2000, 350: 901-907. PMID: 10970807, PMCID: PMC1221325, DOI: 10.1042/bj3500901.Peer-Reviewed Original ResearchConceptsProtein phosphorylationProtein kinasePhosphorylation fluxProtein diffusionSignal transduction pathwaysProtein phosphataseSpherical cellsTransduction pathwaysDifferent cellular geometriesCellular locationPlasma membranePlanar membranesKinaseCell membraneCellular geometryProtein diffusion coefficientsPhosphatasePhosphorylationCell centerProteinMembraneCellsSpatial gradientsCytoplasmPathwayEngineering a Living Cell to Desired Metabolite Concentrations and Fluxes: Pathways with Multifunctional Enzymes
Kholodenko B, Westerhoff H, Schwaber J, Cascante M. Engineering a Living Cell to Desired Metabolite Concentrations and Fluxes: Pathways with Multifunctional Enzymes. Metabolic Engineering 2000, 2: 1-13. PMID: 10935931, DOI: 10.1006/mben.1999.0132.Peer-Reviewed Original ResearchConceptsMultifunctional enzymeRest of metabolismMetabolic engineeringMetabolic control analysisCellular pathwaysCellular metabolismMolecular geneticsCellular enzymesLiving cellsEnzymeMetabolismPathwayGeneticsMachineryMetabolic patternsEnzyme concentrationSingle intermediateModulationCellsMetabolite concentrationsPatterns
1998
Subtleties in control by metabolic channelling and enzyme organization
Kholodenko B, Rohwer J, Cascante M, Westerhoff H. Subtleties in control by metabolic channelling and enzyme organization. Molecular And Cellular Biochemistry 1998, 184: 311-320. PMID: 9746327, DOI: 10.1023/a:1006809028612.Peer-Reviewed Original ResearchConceptsPhosphotransferase systemMetabolic control analysisBacterial phosphotransferase systemEnzyme-enzyme associationsDirect metabolite transferEnzyme organizationConcomitant phosphorylationTernary complex formationPTS pathwayMetabolite transferEnzyme sequestrationMetabolic channellingLiving cellsMacromolecular crowdingPhosphoryl groupEnzyme controlTernary complexCell functionPathwayEnzymeComplex formationIdeal systemEnzyme control coefficientsMetabolic systemsControl coefficientsSubtleties in control by metabolic channelling and enzyme organization
Kholodenko B, Rohwer J, Cascante M, Westerhoff H. Subtleties in control by metabolic channelling and enzyme organization. Developments In Molecular And Cellular Biochemistry 1998, 311-320. DOI: 10.1007/978-1-4615-5653-4_20.Peer-Reviewed Original ResearchPhosphotransferase systemMetabolic control analysisBacterial phosphotransferase systemEnzyme-enzyme associationsDirect metabolite transferEnzyme organizationConcomitant phosphorylationTernary complex formationPTS pathwayMetabolite transferEnzyme sequestrationMetabolic channellingLiving cellsMacromolecular crowdingPhosphoryl groupEnzyme controlTernary complexCell functionPathwayEnzymeComplex formationIdeal systemEnzyme control coefficientsMetabolic systemsControl coefficients
1995
Defining control coefficients in non-ideal metabolic pathways
Kholodenko B, Molenaar D, Schuster S, Heinrich R, Westerhoff H. Defining control coefficients in non-ideal metabolic pathways. Biophysical Chemistry 1995, 56: 215-226. PMID: 17023325, DOI: 10.1016/0301-4622(95)00039-z.Peer-Reviewed Original ResearchMetabolic pathwaysFlux control coefficientsHigh enzyme concentrationsMetabolic control analysisBiochemical pathwaysElemental stepsMetabolite channellingMetabolic channellingRelevant pathwaysEnzyme activityPathwayEnzymeControl coefficientsEnzyme concentrationMoiety-conserved cyclesEqual modulationsSpeciesReverse rateElemental processesModulationActivityComposite control of cell function: metabolic pathways behaving as single control units
Kholodenko B, Schuster S, Rohwer J, Cascante M, Westerhoff H. Composite control of cell function: metabolic pathways behaving as single control units. FEBS Letters 1995, 368: 1-4. PMID: 7615057, DOI: 10.1016/0014-5793(95)00562-n.Peer-Reviewed Original ResearchHow to reveal various aspects of regulation in group-transfer pathways
Kholodenko B, Westerhoff H. How to reveal various aspects of regulation in group-transfer pathways. Biochimica Et Biophysica Acta (BBA) - Bioenergetics 1995, 1229: 275-289. DOI: 10.1016/0005-2728(95)00013-9.Peer-Reviewed Original ResearchGroup-transfer pathwaysEnzyme-enzyme complexPathway componentsGene expressionMetabolic pathwaysAspects of regulationGenetic modulationSpecific inhibitorSuch inhibitorsEnzyme concentrationNon-competitive inhibitorEnzymeControl coefficientsPathwayIntact systemInhibitorsInhibited enzymeRegulationExpression
1993
‘Channelled’ pathways can be more sensitive to specific regulatory signals
Kholodenko B, Demin O, Westerhoff H. ‘Channelled’ pathways can be more sensitive to specific regulatory signals. FEBS Letters 1993, 320: 75-78. PMID: 8462681, DOI: 10.1016/0014-5793(93)81661-i.Peer-Reviewed Original Research