2018
Dissecting RAF Inhibitor Resistance by Structure-based Modeling Reveals Ways to Overcome Oncogenic RAS Signaling
Rukhlenko OS, Khorsand F, Krstic A, Rozanc J, Alexopoulos LG, Rauch N, Erickson KE, Hlavacek WS, Posner RG, Gómez-Coca S, Rosta E, Fitzgibbon C, Matallanas D, Rauch J, Kolch W, Kholodenko BN. Dissecting RAF Inhibitor Resistance by Structure-based Modeling Reveals Ways to Overcome Oncogenic RAS Signaling. Cell Systems 2018, 7: 161-179.e14. PMID: 30007540, PMCID: PMC6149545, DOI: 10.1016/j.cels.2018.06.002.Peer-Reviewed Original ResearchConceptsOncogenic RASERK signalingRAS/ERK pathwayRAF inhibitorsOncogenic Ras signalingMEK/ERKStructure-based modelingRAF inhibitor resistanceRAS mutant tumorsRas signalingPosttranslational modificationsRaf kinaseERK activityRAF dimerizationDrug-protein interactionsERK pathwayMultiple inhibitorsColony formationSignalingMutant NRASCell proliferationDrug designParadoxical activationInhibitor resistanceMechanistic dynamic model
2015
Drug Resistance Resulting from Kinase Dimerization Is Rationalized by Thermodynamic Factors Describing Allosteric Inhibitor Effects
Kholodenko BN. Drug Resistance Resulting from Kinase Dimerization Is Rationalized by Thermodynamic Factors Describing Allosteric Inhibitor Effects. Cell Reports 2015, 12: 1939-1949. PMID: 26344764, DOI: 10.1016/j.celrep.2015.08.014.Peer-Reviewed Original Research
2009
Molecular Dynamics Simulations Reveal that Tyr-317 Phosphorylation Reduces Shc Binding Affinity for Phosphotyrosyl Residues of Epidermal Growth Factor Receptor
Suenaga A, Hatakeyama M, Kiyatkin AB, Radhakrishnan R, Taiji M, Kholodenko BN. Molecular Dynamics Simulations Reveal that Tyr-317 Phosphorylation Reduces Shc Binding Affinity for Phosphotyrosyl Residues of Epidermal Growth Factor Receptor. Biophysical Journal 2009, 96: 2278-2288. PMID: 19289054, PMCID: PMC2717265, DOI: 10.1016/j.bpj.2008.11.018.Peer-Reviewed Original ResearchConceptsSrc homology 2Epidermal growth factor receptorGrowth factor receptorPhospho-tyrosine binding (PTB) domainsLinker regionFull-length ShcPhospho-tyrosine residuesKey conformational changesFactor receptorShc interactionTyr-317Protein ShcTyrosine kinase receptorsPhosphorylated ShcPTB domainRas-mitogenHomology 2Phosphorylation resultsPhosphotyrosyl peptidesProtein kinaseTyrosine phosphorylationBinding domainsSubsequent phosphorylationPhosphotyrosyl residuesShc
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 coefficients
1995
Coenzyme cycles and metabolic control analysis: the determination of the elasticity coefficients from the generalised connectivity theorem.
Kholodenko B, Sauro H, Westerhoff H, Cascante M. Coenzyme cycles and metabolic control analysis: the determination of the elasticity coefficients from the generalised connectivity theorem. IUBMB Life 1995, 35: 615-25. PMID: 7773196.Peer-Reviewed Original ResearchControl theory of metabolic channelling
Kholodenko B, Cascante M, Westerhoff H. Control theory of metabolic channelling. Molecular And Cellular Biochemistry 1995, 143: 151-168. PMID: 7596350, DOI: 10.1007/bf01816949.Peer-Reviewed Original ResearchConceptsControl theory
1994
Control theory of one enzyme
Kholodenko B, Westerhoff H. Control theory of one enzyme. Biochimica Et Biophysica Acta 1994, 1208: 294-305. PMID: 7947961, DOI: 10.1016/0167-4838(94)90116-3.Peer-Reviewed Original ResearchConceptsEnzyme catalytic cycleArbitrary kinetic schemesEnzyme catalyzed reactionsStandard free energy differenceControl of reactionsCatalytic cycleElemental stepsFree energy differenceCatalyzed reactionsFree energy dropForward rate constantElemental transitionsReaction rateEnzyme reactionRate constantsEnergy differenceEnzyme statesKinetic schemeReactionEnzyme cycleSingle enzymeEnzymeStepKineticsConstantsControl theory of metabolic channelling
Kholodenko B, Cascante M, Westerhoff H. Control theory of metabolic channelling. Molecular And Cellular Biochemistry 1994, 133-134: 313-331. PMID: 7808462, DOI: 10.1007/bf01267963.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEnergy MetabolismHumansMitochondria, MuscleModels, BiologicalMusclesPhosphatesSignal TransductionThermodynamicsConceptsControl theory
1993
Metabolic channelling and control of the flux
Kholodenko B, Westerhoff H. Metabolic channelling and control of the flux. FEBS Letters 1993, 320: 71-74. PMID: 8462680, DOI: 10.1016/0014-5793(93)81660-r.Peer-Reviewed Original Research