title: Evaluation of sulfatase-directed quinone methide traps for proteomics.
abstract: Sulfatases hydrolytically cleave sulfate esters through a unique catalytic aldehyde, which is introduced by a posttranslational oxidation. To profile active sulfatases in health and disease, activity-based proteomic tools are needed. Herein, quinone methide (QM) traps directed against sulfatases are evaluated as activity-based proteomic probes (ABPPs). Starting from a p-fluoromethylphenyl sulfate scaffold, enzymatically generated QM-traps can inactivate bacterial aryl sulfatases from Pseudomonas aeruginosa and Klebsiella pneumoniae, and human steroid sulfatase. However, multiple enzyme-generated QMs form, diffuse, and non-specifically label purified enzyme. In complex proteomes, QM labeling is sulfatase-dependent but also non-specific. Thus, fluoromethylphenyl sulfates are poor ABPPs for sulfatases.
authors.affiliation: Bioorganic and Organic Chemistry, Department of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Lenger
authors.forename: Marius
authors.initials: M
authors.lastname: Schröder
authors.forename: Eva C
authors.initials: EC
authors.lastname: Ennemann
authors.forename: Benjamin
authors.initials: B
authors.lastname: Müller
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.forename: Thomas
authors.initials: T
authors.lastname: Noll
authors.forename: Thomas
authors.initials: T
authors.lastname: Dierks
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Hanson
authors.forename: Norbert
authors.initials: N
authors.lastname: Sewald
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D045563:Indolequinones / Q000737:chemistry*; D007711:Klebsiella pneumoniae / Q000201:enzymology; D040901:Proteomics; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013429:Sulfatases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D045563:Indolequinones; C068040:quinone methide; D013429:Sulfatases; D043266:Steryl-Sulfatase