Derek J. Wilson

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Many chemical and biochemical reactions equilibrate within a few seconds of initiation under "native" conditions. To understand the microscopic processes underlying these reactions, the most direct approach is to monitor the reaction as equilibrium is established (i.e. the reaction kinetics). However, this requires the ability to characterize the reaction(More)
We report the use of electrospray ionization (ESI) mass spectrometry (MS) in conjunction with online rapid mixing to monitor the kinetics of acid-induced ferrihemoglobin denaturation. Under equilibrium conditions, the hemoglobin mass spectrum is dominated by the intact heterotetramer. Dimeric and monomeric species are also observed at lower intensities. In(More)
Electrospray ionization (ESI) mass spectrometry is a powerful and versatile tool for proteomic analysis. By understanding how proteins and peptides behave during ESI, it is possible to predict source conditions that will maximize ionization efficiency, ultimately leading to lower detection limits for protein identification and more accurate quantitation. In(More)
An electrospray coupled microfluidic reactor for the measurement of millisecond time-scale, solution phase kinetics is introduced. The device incorporates a simple two-channel design that is etched into polymethyl methacrylate (PMMA) by laser ablation. The outlet of the device is laser cut to a sharp tip, facilitating low dead volume 'on chip' electrospray.(More)
It remains an open question as to whether experiments involving collision-induced dissociation (CID) can provide a viable approach for monitoring spatially resolved deuteration levels in electrosprayed polypeptide ions. A number of laboratories reported the successful application of CID following solution-phase H/D exchange (HDX), whereas others found that(More)
This work introduces an integrated microfluidic device for measuring rapid H/D exchange (HDX) in proteins. By monitoring backbone amide HDX on the millisecond to low second time scale, we are able to characterize conformational dynamics in weakly structured regions, such as loops and molten globule-like domains that are inaccessible in conventional HDX(More)
A novel continuous-flow apparatus for on-line kinetic studies of (bio)chemical solution-phase processes by electrospray ionization mass spectrometry (ESI-MS) is described. The device is based on two concentric capillaries. Fluid is released from the inner capillary into the intercapillary space, where it mixes with solution flowing through the outer(More)
Mutations in the BCR-ABL1 kinase domain are an established mechanism of tyrosine kinase inhibitor (TKI) resistance in Philadelphia chromosome-positive leukemia, but fail to explain many cases of clinical TKI failure. In contrast, it is largely unknown why some patients fail TKI therapy despite continued suppression of BCR-ABL1 kinase activity, a situation(More)
The inducible nitric oxide synthase core oxygen domain (iNOS(COD)) is a homodimeric protein complex of ca. 100 kDa. In this work, the subunit disassembly and unfolding of the protein following a pH jump from 7.5 to 2.8 were monitored by on-line rapid mixing in conjunction with electrospray (ESI) time-of-flight mass spectrometry. Various protein species(More)
Concerted efforts were directed towards understanding the control of acetohydroxy acid synthase (AHAS) in the gyrB mutant hisU1820 of Salmonella typhimurium. A media shift from valine to valine plus isoleucine causes a dramatic 4 to 5 fold burst of AHAS valine sensitive activity which appears to be dependent on translation. DJ19, an isolated valine(More)