2025
Structure of a mutated photosystem II complex reveals changes to the hydrogen-bonding network that affect proton egress during O–O bond formation
Flesher D, Shin J, Debus R, Brudvig G. Structure of a mutated photosystem II complex reveals changes to the hydrogen-bonding network that affect proton egress during O–O bond formation. Journal Of Biological Chemistry 2025, 301: 108272. PMID: 39922494, PMCID: PMC11930075, DOI: 10.1016/j.jbc.2025.108272.Peer-Reviewed Original ResearchHydrogen bond networkProton egressWater moleculesO-O bond formationPhotosystem IIO-O bondStructure of photosystem IIHydrogen-bonded channelsWater-splitting enzymeRelease O<sub>2</sub> anProton egress pathwaysProton transferHydrogen bondsBond formationPhotosystem II complexSite-directed mutagenesisOxygen evolution rateReaction mechanismAmino groupsSide chainsCryo-EM structureCatalytic turnoverChloride ionsWater-protein interactionsD2 subunits
2024
Structural study for substrate recognition of human N‐terminal glutamine amidohydrolase 1 in the arginine N‐degron pathway
Kang J, Park J, Lee J, Jang J, Han B. Structural study for substrate recognition of human N‐terminal glutamine amidohydrolase 1 in the arginine N‐degron pathway. Protein Science 2024, 33: e5067. PMID: 38864716, PMCID: PMC11168063, DOI: 10.1002/pro.5067.Peer-Reviewed Original ResearchConceptsN-degron pathwaySubstrate recognitionN-degronSubstrate-binding conformationHalf-life of proteinsProtein degradation machineryTargeted protein therapyDegradation machinerySubstrate specificityProtein regulationBackbone of proteinsGln residuesCharged residuesNT residuesDegradation systemProteinBiochemical analysisResiduesPathwayStructural studiesGlnProtein therapyArginineSide chainsShed light
2023
Substrate-independent activation pathways of the CRISPR-Cas9 HNH nuclease
Wang J, Maschietto F, Qiu T, Arantes P, Skeens E, Palermo G, Lisi G, Batista V. Substrate-independent activation pathways of the CRISPR-Cas9 HNH nuclease. Biophysical Journal 2023, 122: 4635-4644. PMID: 37936350, PMCID: PMC10754686, DOI: 10.1016/j.bpj.2023.11.005.Peer-Reviewed Original ResearchConceptsHNH domainHNH nucleaseHigh fidelity enzymesInduced-fit mechanismActivation pathwayActive stateMolecular dynamics trajectoriesCognate substratesConformation 2Conformational selectionObligate stepAla mutantBackbone amidesΑ-helixSide chainsSingle LysEssential roleNucleasePathwayDynamics trajectoriesResiduesConformationMutantsInterconversion pathwaysCRISPR
2022
Imine Directed Cp*RhIII‐Catalyzed N−H Functionalization and Annulation with Amino Amides, Aldehydes, and Diazo Compounds
Zoll A, Molas J, Mercado B, Ellman J. Imine Directed Cp*RhIII‐Catalyzed N−H Functionalization and Annulation with Amino Amides, Aldehydes, and Diazo Compounds. Angewandte Chemie 2022, 135 DOI: 10.1002/ange.202210822.Peer-Reviewed Original ResearchDiazo compoundsAmino amidesX-ray crystallographic characterizationFive-membered rhodacycleAmino acid side chainsAcid side chainsRange of functionalitiesCrystallographic characterizationAlkyl aldehydesSide chainsEfficient reactantsFunctionalizationMinimal racemizationFirst exampleMechanistic studiesIminesAldehydesAnnulationAmidesEfficient transformationCompoundsCatalyzedPiperazinonesRhodacycleReactantsImine Directed Cp*RhIII‐Catalyzed N−H Functionalization and Annulation with Amino Amides, Aldehydes, and Diazo Compounds
Zoll A, Molas J, Mercado B, Ellman J. Imine Directed Cp*RhIII‐Catalyzed N−H Functionalization and Annulation with Amino Amides, Aldehydes, and Diazo Compounds. Angewandte Chemie International Edition 2022, 62: e202210822. PMID: 36331194, PMCID: PMC9805510, DOI: 10.1002/anie.202210822.Peer-Reviewed Original ResearchConceptsDiazo compoundsH functionalizationAmino amidesX-ray crystallographic characterizationFive-membered rhodacycleAmino acid side chainsAcid side chainsRange of functionalitiesCrystallographic characterizationAlkyl aldehydesSide chainsEfficient reactantsFunctionalizationMinimal racemizationFirst exampleMechanistic studiesIminesAldehydesAnnulationEfficient transformationAmidesCompoundsCatalyzedPiperazinonesRhodacycleTools for analyzing protonation states and for tracing proton transfer pathways with examples from the Rb. sphaeroides photosynthetic reaction centers
Wei R, Khaniya U, Mao J, Liu J, Batista V, Gunner M. Tools for analyzing protonation states and for tracing proton transfer pathways with examples from the Rb. sphaeroides photosynthetic reaction centers. Photosynthesis Research 2022, 156: 101-112. PMID: 36307598, DOI: 10.1007/s11120-022-00973-0.Peer-Reviewed Original ResearchConceptsProtonation stateMolecular dynamicsProton affinityReaction centersSide chainsElectron transfer reactionsProton transfer pathwayHydroxy side chainsBacterial reaction centersProton-transfer networkPhotosynthetic reaction centersChains of waterGrotthuss mechanismTransfer reactionsActive siteTransfer pathwayQB siteProton bindingProtein conformationTransmembrane electrochemical gradient
2021
Structure of a monomeric photosystem II core complex from a cyanobacterium acclimated to far-red light reveals the functions of chlorophylls d and f
Gisriel CJ, Shen G, Ho MY, Kurashov V, Flesher DA, Wang J, Armstrong WH, Golbeck JH, Gunner MR, Vinyard DJ, Debus RJ, Brudvig GW, Bryant DA. Structure of a monomeric photosystem II core complex from a cyanobacterium acclimated to far-red light reveals the functions of chlorophylls d and f. Journal Of Biological Chemistry 2021, 298: 101424. PMID: 34801554, PMCID: PMC8689208, DOI: 10.1016/j.jbc.2021.101424.Peer-Reviewed Original ResearchConceptsChl f moleculesWater oxidationF moleculesPhotosystem II core complexII core complexesPhotosystem IIÅ resolution cryo-EM structureFar-red light photoacclimationResolution cryo-EM structurePhotochemical catalysisElectron transfer chainCryo-EM structureGlutamate side chainVisible lightCore complexSide chainsRed limitD moleculesSolar energy utilizationAcceptor sidePSII biogenesisFar-red lightPCC 7335Core subunitsMoleculesCryo-EM structures of Escherichia coli cytochrome bo3 reveal bound phospholipids and ubiquinone-8 in a dynamic substrate binding site
Li J, Han L, Vallese F, Ding Z, Choi SK, Hong S, Luo Y, Liu B, Chan CK, Tajkhorshid E, Zhu J, Clarke O, Zhang K, Gennis R. Cryo-EM structures of Escherichia coli cytochrome bo3 reveal bound phospholipids and ubiquinone-8 in a dynamic substrate binding site. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2106750118. PMID: 34417297, PMCID: PMC8403832, DOI: 10.1073/pnas.2106750118.Peer-Reviewed Original ResearchConceptsHydrogen bondsMembrane scaffold protein (MSP) nanodiscsSide chainsMetal redox centerCryo-EM structureInternal water moleculesEscherichia coli cytochrome bo3Facilitate proton transferImidazole side chainIsoprene side chainAccess of waterCryogenic electron microscopyRedox centersWater moleculesProton transferSubunit IAqueous phaseConformation 1Respiratory cytochromesRelated cytochromesHydrophobic grooveUbiquinol oxidaseQuinol oxidaseCytochrome bo3Computational studyAn epilepsy-causing mutation leads to co-translational misfolding of the Kv7.2 channel
Urrutia J, Aguado A, Gomis-Perez C, Muguruza-Montero A, Ballesteros OR, Zhang J, Nuñez E, Malo C, Chung HJ, Leonardo A, Bergara A, Villarroel A. An epilepsy-causing mutation leads to co-translational misfolding of the Kv7.2 channel. BMC Biology 2021, 19: 109. PMID: 34020651, PMCID: PMC8138981, DOI: 10.1186/s12915-021-01040-1.Peer-Reviewed Original ResearchConceptsKv7.2 channelsChannel functionSequences of proteinsNon-native configurationsNascent chainsProper foldingEpilepsy-causing mutationsIQ motifResponsive domainHuman diseasesHelix ANative conformationFolding routeIon channelsKCNQ2 geneMutationsNeuronal compartmentsFoldingMisfoldingProteinKey pathogenic mechanismsPathogenic variantsSilico studiesPathogenic mechanismsSide chains
2019
Mechanism of actin polymerization revealed by cryo-EM structures of actin filaments with three different bound nucleotides
Chou SZ, Pollard TD. Mechanism of actin polymerization revealed by cryo-EM structures of actin filaments with three different bound nucleotides. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 4265-4274. PMID: 30760599, PMCID: PMC6410863, DOI: 10.1073/pnas.1807028115.Peer-Reviewed Original ResearchConceptsATP hydrolysisActin filamentsBarbed endsMultiple favorable interactionsCryo-electron microscopyNetwork of interactionsShort-pitch helixActin polymerizationC-terminusAdjacent subunitsSubdomain 2Conformational changesEM structuresBinding loopSubdomain 3SubunitsPhosphate dissociationPointed endRelease sitesFilamentsActive siteConformationADPBackbone conformationSide chainsCrystallographic identification of spontaneous oxidation intermediates and products of protein sulfhydryl groups
Wang J. Crystallographic identification of spontaneous oxidation intermediates and products of protein sulfhydryl groups. Protein Science 2019, 28: 472-477. PMID: 30592103, PMCID: PMC6371210, DOI: 10.1002/pro.3568.Peer-Reviewed Original ResearchConceptsLys side chainsSide chainsO bridgesChemical identificationCrystal structureElectron density featuresCross-linking speciesCys side chainDirect chemical identificationProtein crystal structuresMass spectrometric analysisOxidation intermediatesCys-245Primary aminesMethylene groupCrystallographic identificationSpectrometric analysisDehydration mechanismLys-158Protein sulfhydryl groupsSulfhydryl groupsProtein structureChainCHCys residues
2018
Rapid phenolic O-glycosylation of small molecules and complex unprotected peptides in aqueous solvent
Wadzinski TJ, Steinauer A, Hie L, Pelletier G, Schepartz A, Miller SJ. Rapid phenolic O-glycosylation of small molecules and complex unprotected peptides in aqueous solvent. Nature Chemistry 2018, 10: 644-652. PMID: 29713033, PMCID: PMC5964040, DOI: 10.1038/s41557-018-0041-8.Peer-Reviewed Original ResearchConceptsUnprotected peptidesSmall moleculesAmino acid functionalitiesHigh functional group toleranceFunctional group toleranceFree synthesisAcid functionalityProteinogenic amino acidsAqueous solventSelective formationSynthetic glycopeptidesAnomeric productsPhenolic functionalityGroup toleranceNatural productsGood yieldsSide chainsGlycosyl donorsBiochemical probesAryl glycosidesRoom temperatureMoleculesO-glycosylationPeptidesSimple approachComparing side chain packing in soluble proteins, protein‐protein interfaces, and transmembrane proteins
Gaines JC, Acebes S, Virrueta A, Butler M, Regan L, O'Hern CS. Comparing side chain packing in soluble proteins, protein‐protein interfaces, and transmembrane proteins. Proteins Structure Function And Bioinformatics 2018, 86: 581-591. PMID: 29427530, PMCID: PMC5912992, DOI: 10.1002/prot.25479.Peer-Reviewed Original ResearchConceptsProtein-protein interfacesClass of proteinsTransmembrane proteinSoluble proteinSolvent-inaccessible coreMembrane proteinsProtein classesCore residuesProtein-protein interactionsHigh-resolution crystal structuresHydrophobic core mutationsRelative solvent accessibilityAnalysis of mutationsSide-chain packingProtein complexesNon-core regionsSolvent accessibilityProteinSide-chain conformationsCore mutationsMutationsResiduesSide chains
2017
Sequence-Selective Binding of Oligopeptides in Water through Hydrophobic Coding
Awino JK, Gunasekara RW, Zhao Y. Sequence-Selective Binding of Oligopeptides in Water through Hydrophobic Coding. Journal Of The American Chemical Society 2017, 139: 2188-2191. PMID: 28128940, PMCID: PMC5310974, DOI: 10.1021/jacs.6b12949.Peer-Reviewed Original ResearchHighly Efficient Synthetic Method on Pyroacm Resin Using the Boc SPPS Protocol for C‐terminal Cysteine Peptide Synthesis
Juvekar V, Kim K, Gong Y. Highly Efficient Synthetic Method on Pyroacm Resin Using the Boc SPPS Protocol for C‐terminal Cysteine Peptide Synthesis. Bulletin Of The Korean Chemical Society 2017, 38: 54-62. DOI: 10.1002/bkcs.11045.Peer-Reviewed Original ResearchSolid-phase peptide synthesisPeptide synthesisSide chainsCleavage of protecting groupsSynthesis of model peptidesCysteine side chainsBoc protocolTrifluoromethanesulfonic acidSPPS protocolsSynthetic methodCleavage conditionsModel peptidesModification reactionsEster peptideBocSynthesisTFMSAC-terminal cysteineChainA-factorSPPS
2016
A Mechanistic Model for Colibactin-Induced Genotoxicity
Healy AR, Nikolayevskiy H, Patel JR, Crawford JM, Herzon SB. A Mechanistic Model for Colibactin-Induced Genotoxicity. Journal Of The American Chemical Society 2016, 138: 15563-15570. PMID: 27934011, PMCID: PMC5359767, DOI: 10.1021/jacs.6b10354.Peer-Reviewed Original ResearchConceptsGene clusterE. coliDNA double-strand breaksDouble-strand breaksProbiotic Nissle 1917Clb gene clusterEukaryotic cellsCertain commensalDNA bindingProbiotic E. coliDisparate phenotypesPrecolibactinsAlkylate DNAColibactinIsolation effortsFermentation productsColiDNA alkylationDNANissle 1917Mechanistic modelSide chainsNatural productsMetabolite structuresEfficient DNA alkylationNa+ coordination at the Na2 site of the Na+/I− symporter
Ferrandino G, Nicola JP, Sánchez YE, Echeverria I, Liu Y, Amzel LM, Carrasco N. Na+ coordination at the Na2 site of the Na+/I− symporter. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e5379-e5388. PMID: 27562170, PMCID: PMC5027462, DOI: 10.1073/pnas.1607231113.Peer-Reviewed Original ResearchConceptsNa2 siteActive I(-) transportThyroid hormone biosynthesisSodium/iodide symporterSLC5 familyGreat medical relevanceSame foldPlasma membraneHormone biosynthesisDependent transportersSimilar functionsMedical relevanceTransportersMechanistic insightsWhole cellsBinding sitesResiduesSymporterI- transportS353Side chainsT354SitesBiosynthesisIons bindCellular Activity of New Small Molecule Protein Arginine Deiminase 3 (PAD3) Inhibitors
Jamali H, Khan HA, Tjin CC, Ellman JA. Cellular Activity of New Small Molecule Protein Arginine Deiminase 3 (PAD3) Inhibitors. ACS Medicinal Chemistry Letters 2016, 7: 847-851. PMID: 27660689, PMCID: PMC5018872, DOI: 10.1021/acsmedchemlett.6b00215.Peer-Reviewed Original ResearchProtein arginine deiminasesThapsigargin-induced cell deathPost-translational deiminationHEK293T cellsArginine side chainHuman disease statesInhibitor 2Cellular activitiesCell deathPAD isozymesArginine deiminasesCell growthPAD activityPAD3Representative inhibitorsDisease statesNeurodegenerative responseSide chainsInhibitorsDeiminationApoptosisIsozymesActivityFirst timeCell activityUnderstanding the physical basis for the side‐chain conformational preferences of methionine
Virrueta A, O'Hern CS, Regan L. Understanding the physical basis for the side‐chain conformational preferences of methionine. Proteins Structure Function And Bioinformatics 2016, 84: 900-911. PMID: 26917446, DOI: 10.1002/prot.25026.Peer-Reviewed Original ResearchConceptsSide-chain dihedral angle distributionsAmino acidsHigh-resolution protein crystal structuresProtein-protein interfacesMet side chainsStructure of MetProtein crystal structuresVersatile amino acidDihedral angle distributionsProtein structureProtein coreIleSide chainsLeuValPheAcidThrObserved distributionCrystal structureMetSMethionineSerTyrSelenomethionineThe Role of Electrostatic Interactions in Folding of β‑Proteins
Davis CM, Dyer RB. The Role of Electrostatic Interactions in Folding of β‑Proteins. Journal Of The American Chemical Society 2016, 138: 1456-1464. PMID: 26750867, PMCID: PMC4749129, DOI: 10.1021/jacs.5b13201.Peer-Reviewed Original ResearchConceptsElectrostatic interactionsAmide I regionAtomic-level molecular dynamics simulationsProtonation stateExtended β-sheet structureRelaxation dynamicsAspartic acid side chainMolecular dynamics simulationsΒ-sheet formΒ-sheet structureAcid side chainsFTIR spectroscopyPin1 WW domainPeptide backboneWW domainsAspartic acidSide chainsNegative chargeΒ-turnDynamics simulationsGood agreementTurn stabilitySimulation predictionsSpectroscopyΒ-sheet
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