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
2007
Epidermal Growth Factor Receptor Mutants from Human Lung Cancers Exhibit Enhanced Catalytic Activity and Increased Sensitivity to Gefitinib
Mulloy R, Ferrand A, Kim Y, Sordella R, Bell D, Haber D, Anderson K, Settleman J. Epidermal Growth Factor Receptor Mutants from Human Lung Cancers Exhibit Enhanced Catalytic Activity and Increased Sensitivity to Gefitinib. Cancer Research 2007, 67: 2325-2330. PMID: 17332364, DOI: 10.1158/0008-5472.can-06-4293.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorEpidermal growth factor receptor mutantMultiple levels in vivoIn vitro kinase assayEpidermal growth factor receptor functionPurified recombinant proteinWild-type epidermal growth factor receptorSensitivity to kinase inhibitionNon-small cell lung cancerCOOH-terminal tyrosineHuman non-small cell lung cancerIncreased sensitivity to gefitinibSensitivity to gefitinibCell lung cancerAutophosphorylation activityGrowth factor receptorCell-based studiesEGFR kinase inhibitorsCytoplasmic domainRecombinant proteinsKinase assayEnzyme functionDownstream effectorsMutantsKinase activity
2002
Mechanistic Characterization of Toxoplasma gondiiThymidylate Synthase (TS-DHFR)-Dihydrofolate Reductase EVIDENCE FOR A TS INTERMEDIATE AND TS HALF-SITES REACTIVITY*
Johnson E, Hinz W, Atreya C, Maley F, Anderson K. Mechanistic Characterization of Toxoplasma gondiiThymidylate Synthase (TS-DHFR)-Dihydrofolate Reductase EVIDENCE FOR A TS INTERMEDIATE AND TS HALF-SITES REACTIVITY*. Journal Of Biological Chemistry 2002, 277: 43126-43136. PMID: 12192007, DOI: 10.1074/jbc.m206523200.Peer-Reviewed Original Research
2000
An analysis of the catalytic cycle of HIV-1 reverse transcriptase: opportunities for chemotherapeutic intervention based on enzyme inhibition.
Furman P, Painter G, Anderson K. An analysis of the catalytic cycle of HIV-1 reverse transcriptase: opportunities for chemotherapeutic intervention based on enzyme inhibition. Current Pharmaceutical Design 2000, 6: 547-67. PMID: 10788596, DOI: 10.2174/1381612003400777.Peer-Reviewed Original ResearchConceptsCatalytic cycleIntrinsic binding affinityHIV-1 reverse transcriptaseCatalytic complexChemical catalysisBinding affinityCatalysisMolecular forcesReverse transcriptase inhibitorsAllosteric siteClasses of approved drugsNon-nucleoside reverse transcriptase inhibitorsTranscriptase inhibitorsNucleoside reverse transcriptase inhibitorsSite of inhibitionEnzyme inhibitionReverse transcriptaseAlternative substratesEnzyme
1999
[6] Fundamental mechanisms of substrate channeling
Anderson K. [6] Fundamental mechanisms of substrate channeling. Methods In Enzymology 1999, 308: 111-145. PMID: 10507003, DOI: 10.1016/s0076-6879(99)08008-8.Peer-Reviewed Original ResearchAnimalsBinding SitesCarbamoyl-Phosphate Synthase (Ammonia)Citrate (si)-SynthaseDiffusionDimerizationGlycerophosphatesIndolesKineticsLeishmania majorMagnetic Resonance SpectroscopyMalate DehydrogenaseModels, MolecularMultienzyme ComplexesMutationPeptide SynthasesProtein ConformationSalmonella typhimuriumTetrahydrofolate DehydrogenaseThymidylate SynthaseTryptophan Synthase
1998
Substrate Channeling and Domain−Domain Interactions in Bifunctional Thymidylate Synthase−Dihydrofolate Reductase †
Liang P, Anderson K. Substrate Channeling and Domain−Domain Interactions in Bifunctional Thymidylate Synthase−Dihydrofolate Reductase †. Biochemistry 1998, 37: 12195-12205. PMID: 9724533, DOI: 10.1021/bi9803168.Peer-Reviewed Original ResearchConceptsDHFR active siteActive siteTS active siteCrystal structureTransient kinetic analysisEnzyme active siteBifunctional TS-DHFRProtein surfaceTS-DHFRKinetics of substrateReductase enzymeSingle polypeptide chainKinetic analysisDihydrofolateThymidylate synthasePolypeptide chainSubstrateEnzymeStructureDomain-domain interactionsSpecies of protozoaInteractionKineticsL. majorChainKinetic Reaction Scheme for the Dihydrofolate Reductase Domain of the Bifunctional Thymidylate Synthase−Dihydrofolate Reductase from Leishmania major †
Liang P, Anderson K. Kinetic Reaction Scheme for the Dihydrofolate Reductase Domain of the Bifunctional Thymidylate Synthase−Dihydrofolate Reductase from Leishmania major †. Biochemistry 1998, 37: 12206-12212. PMID: 9724534, DOI: 10.1021/bi9803170.Peer-Reviewed Original ResearchConceptsThymidylate synthase-dihydrofolate reductaseKinetic reaction schemeCatalytic activityDihydrofolate reductaseBifunctional enzymeReaction schemeBifunctional thymidylate synthase-dihydrofolate reductaseE. coli enzymeSynthase-dihydrofolate reductaseSteady-state turnoverDihydrofolate reductase domainState kinetic methodsSingle polypeptide chainEnzyme dihydrofolate reductaseSpecies of protozoaReaction pathwaysRelease of productsColi enzymeParasite Leishmania majorMonofunctional formsDihydrofolate reductase activityReductase domainConformational changesKinetic stepsPolypeptide chainLeishmania major Pteridine Reductase 1 Belongs to the Short Chain Dehydrogenase Family: Stereochemical and Kinetic Evidence †
Luba J, Nare B, Liang P, Anderson K, Beverley S, Hardy L. Leishmania major Pteridine Reductase 1 Belongs to the Short Chain Dehydrogenase Family: Stereochemical and Kinetic Evidence †. Biochemistry 1998, 37: 4093-4104. PMID: 9521731, DOI: 10.1021/bi972693a.Peer-Reviewed Original Research
1995
Crystallization and preliminary X‐ray investigation of the recombinant Trypanosoma brucei rhodesiense calmodulin
El‐Sayed N, Patton C, Harkins P, Fox R, Anderson K. Crystallization and preliminary X‐ray investigation of the recombinant Trypanosoma brucei rhodesiense calmodulin. Proteins Structure Function And Bioinformatics 1995, 21: 354-357. PMID: 7567957, DOI: 10.1002/prot.340210409.Peer-Reviewed Original ResearchConceptsPreliminary X-ray investigationUnit cell dimensionsMolecular replacement methodX-ray investigationsSpace groupAsymmetric unitCrystal structureCell dimensionsRecombinant calmodulinMolecular massCrystalUnit cellTrypanosoma brucei rhodesienseVapor diffusionReplacement methodM cacodylate bufferCalmodulinStructure