2023
Design of a mucin-selective protease for targeted degradation of cancer-associated mucins
Pedram K, Shon D, Tender G, Mantuano N, Northey J, Metcalf K, Wisnovsky S, Riley N, Forcina G, Malaker S, Kuo A, George B, Miller C, Casey K, Vilches-Moure J, Ferracane M, Weaver V, Läubli H, Bertozzi C. Design of a mucin-selective protease for targeted degradation of cancer-associated mucins. Nature Biotechnology 2023, 42: 597-607. PMID: 37537499, PMCID: PMC11018308, DOI: 10.1038/s41587-023-01840-6.Peer-Reviewed Original ResearchCancer progressionSpecific protein glycoformsUndruggable proteinsTargeted degradationProtein degradationBreast cancer progressionCell surface bindingSubstrate selectivityCell-type selectivityCell deathGlycan motifsProtein glycoformsDiscrete peptidesCancer cellsProteinCulture modelProteaseTarget cellsTumor growthCancer-associated mucinsCellsMouse modelDegradersGrowthMotif
2021
Classification, structural biology, and applications of mucin domain-targeting proteases
Shon DJ, Kuo A, Ferracane MJ, Malaker SA. Classification, structural biology, and applications of mucin domain-targeting proteases. Biochemical Journal 2021, 478: 1585-1603. PMID: 33909028, DOI: 10.1042/bcj20200607.Peer-Reviewed Original ResearchConceptsClass of proteinsHost-microbe interfaceImmunoglobulin A (IgA) proteaseThreonine residuesGlycan repertoireStructural biologyDistinct bacteriaGlycan structuresSource of nutrientsHinge regionProteaseIgA proteaseIntricate interplayMucosal environmentColonizationStructural featuresMutualistsMucosal colonizationEpithelial surfaceBacterial colonizationMicrobesTranslocation of microbes
2019
The mucin-selective protease StcE enables molecular and functional analysis of human cancer-associated mucins
Malaker SA, Pedram K, Ferracane MJ, Bensing BA, Krishnan V, Pett C, Yu J, Woods EC, Kramer JR, Westerlind U, Dorigo O, Bertozzi CR. The mucin-selective protease StcE enables molecular and functional analysis of human cancer-associated mucins. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 7278-7287. PMID: 30910957, PMCID: PMC6462054, DOI: 10.1073/pnas.1813020116.Peer-Reviewed Original ResearchConceptsModular protein domainsProtein domainsSecreted proteinsMucin domainFunctional analysisHuman diseasesMucin biologyGlycosylation patternsCultured cellsMolecular levelCell surfaceSequence coverageKey playersBacterial proteasesCancer-associated mucinsDiscrete peptidesBiological ligandsProteaseHuman mucinsGlycoform analysisStcESiglec-9Domain structureMass spectrometryDomain