2021
Structure-guided design of a perampanel-derived pharmacophore targeting the SARS-CoV-2 main protease
Deshmukh MG, Ippolito JA, Zhang CH, Stone EA, Reilly RA, Miller SJ, Jorgensen WL, Anderson KS. Structure-guided design of a perampanel-derived pharmacophore targeting the SARS-CoV-2 main protease. Structure 2021, 29: 823-833.e5. PMID: 34161756, PMCID: PMC8218531, DOI: 10.1016/j.str.2021.06.002.Peer-Reviewed Original ResearchConceptsMain proteaseSARS-CoV-2 main proteaseActive site flexibilityDetailed structural insightsStructure-activity relationshipsInhibitor design effortsLow micromolar rangeActive site cysteineChemical scaffoldsLow nanomolar rangeCovalent adductsStructure-guided designCrystal structureStructural insightsPharmacophoreAdductsAttractive targetScaffoldsCysteineAnaloguesMechanism of actionSupRangeStructure
2019
Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents
Perov S, Lidor O, Salinas N, Golan N, Fligelman E, Deshmukh M, Willbold D, Landau M. Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents. PLOS Pathogens 2019, 15: e1007978. PMID: 31469892, PMCID: PMC6748439, DOI: 10.1371/journal.ppat.1007978.Peer-Reviewed Original ResearchConceptsDisease-associated amyloidsStructural insightsCross-seeded fibrillationMajor curli subunitBiofilm formationHost cell adhesionCurli amyloid fibrilsAmyloid-forming segmentAlzheimer's disease-associated amyloidAnti-amyloid compoundsCurli formationCurli subunitsPathological amyloidsAmyloidogenic regionsMicrobial sourcesEnvironmental stressorsAmyloid interactionsCell adhesionAnti-biofilm agentsΒ-sheetCsgANeurodegenerative diseasesSalmonella typhimuriumStructural linkStructural resemblance
2016
The BR domain of PsrP interacts with extracellular DNA to promote bacterial aggregation; structural insights into pneumococcal biofilm formation
Schulte T, Mikaelsson C, Beaussart A, Kikhney A, Deshmukh M, Wolniak S, Pathak A, Ebel C, Löfling J, Fogolari F, Henriques-Normark B, Dufrêne YF, Svergun D, Nygren PÅ, Achour A. The BR domain of PsrP interacts with extracellular DNA to promote bacterial aggregation; structural insights into pneumococcal biofilm formation. Scientific Reports 2016, 6: 32371. PMID: 27582320, PMCID: PMC5007671, DOI: 10.1038/srep32371.Peer-Reviewed Original ResearchConceptsPneumococcal biofilm formationBiofilm formationExtracellular DNAPneumococcal serine-rich repeat proteinRich repeat proteinElectrophoretic mobility shift assaysHuman pathogen Streptococcus pneumoniaeAdhesive matrix moleculesMobility shift assaysMicrobial surface componentsMajor human pathogen Streptococcus pneumoniaeN-terminal regionNon-globular structuresSerine-rich repeat proteinPathogen Streptococcus pneumoniaeHelical DNA structureRepeat proteinsHeterologous expressionCircular dichroism studiesBR domainShift assaysStructural insightsBiofilm matrixIntermolecular β-sheetsBacterial aggregation