2017
Understanding the molecular mechanism of substrate channeling and domain communication in protozoal bifunctional TS-DHFR
Anderson K. Understanding the molecular mechanism of substrate channeling and domain communication in protozoal bifunctional TS-DHFR. Protein Engineering Design And Selection 2017, 30: 253-261. PMID: 28338744, PMCID: PMC6438133, DOI: 10.1093/protein/gzx004.Peer-Reviewed Original ResearchConceptsBifunctional thymidylate synthase-dihydrofolate reductaseThymidylate synthase-dihydrofolate reductaseSubstrate channelingDihydrofolate reductaseN-terminal amino acid extensionAmino acid extensionDihydrofolate reductase domainThymidylate synthaseFolate metabolizing enzymesAcid extensionMonofunctional formsPolypeptide chainMutation analysisMolecular mechanismsMetabolic enzymesParasitic protozoaDNA synthesisFunctional regionsInhibitor designSpeciesEnzymeStructural similarityStructural studiesEfficient catalysisLeishmania major
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 ResearchThe Kinetic Mechanism of the Human Bifunctional Enzyme ATIC (5-Amino-4-imidazolecarboxamide Ribonucleotide Transformylase/Inosine 5′-Monophosphate Cyclohydrolase) A SURPRISING LACK OF SUBSTRATE CHANNELING*
Bulock K, Beardsley G, Anderson K. The Kinetic Mechanism of the Human Bifunctional Enzyme ATIC (5-Amino-4-imidazolecarboxamide Ribonucleotide Transformylase/Inosine 5′-Monophosphate Cyclohydrolase) A SURPRISING LACK OF SUBSTRATE CHANNELING*. Journal Of Biological Chemistry 2002, 277: 22168-22174. PMID: 11948179, DOI: 10.1074/jbc.m111964200.Peer-Reviewed Original ResearchConceptsCyclohydrolase reactionProduction of inosine monophosphateRelease of tetrahydrofolateSteady-state kinetic techniquesStopped-flow absorbanceBifunctional enzymeActive siteBifunctional proteinSubstrate channelingInosine 5'-monophosphateCyclohydrolaseEnzymatic activityChemotherapeutic targetEnzyme reaction pathwayInosine monophosphateKinetic mechanismFormyltransferaseProteinEnzymeKinetic analysisPathwayKinetic advantageKinetic evidenceKinetic techniquesRibonucleotides
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 chainStructure and Functional Relationships in Human pur H
Beardsley G, Rayl E, Gunn K, Moroson B, Seow H, Anderson K, Vergis J, Fleming K, Worland S, Condon B, Davies J. Structure and Functional Relationships in Human pur H. Advances In Experimental Medicine And Biology 1998, 431: 221-226. PMID: 9598063, DOI: 10.1007/978-1-4615-5381-6_43.Peer-Reviewed Original Research