Educational Background: |
PhD, Cornell University, 1950
BS, University of Nebraska, 1943
DSc (hon), Universities of Nebraska , Liege, Purdue |
Awards: |
•US Army: Combat Infantry Badge, Purple Heart, Presidential Unit Citation, Five Bronze Star Medals
•National Academy of Sciences
•American Academy of Arts and Sciences
•Italian Academy of Sciences, XL
•American Chemical Society: Analytical Chemistry; Chemical Instrumentation; Mass Spectrometry; Nichols Gold Medal
•Spectroscopy Society of Pittsburgh Award
•Anachem Award
•Pittsburgh Analytical Chemistry Award
•Chemical Pioneer Award, American Institute of Chemists
•Sir J. J. Thomson Gold Medal
•University of Naples Gold Medal
•Robert Boyle Gold Medal, Royal Society of Chemistry
•Bijvoet Medal, Utrecht University
•Heyrovsky Medal, Czech Academy of Sciences
•Giulio Natta Gold Medal, Italian Chemical Society
•Torbern Bergman Medal, Swedish Chemical Society
•Distinguished Contribution in Mass Spectromety Award, American Society for Mass Spectrometry
•Lavoisier Medal, French Chemical Society
•Pehr Edman Award, International Association of Protein Structure Analysis and Proteomics |
Research Description: |
Our research in molecular mass spectrometry (MS) involves theory, mechanisms, instrumentation, computerization, and applications to polymers and biomolecules. Our "top-down" proteomics technique for MS/MS characterization of proteins that combines Fourier-transform mass spectrometry (FTMS) with electrospray ionization (ESI) now includes our "electron capture dissociation (ECD)" to provide far higher specificity for localization of posttranslational modifications, such as glycosylation, oxidation, and proteolysis. We have recently extended the top-down technique limit from ~50 kDa proteins to those >200 kDa.
We have pioneered the study of gas phase protein ion conformations. H/D exchange indicates exposed regions of these ions. "Native electron capture dissociation” provides details of native conformation unfolding during solvent removal after ESI. For gaseous protein ions, ECD yields direct conformational characterization, as it only cleaves backbone bonds without affecting tertiary non-covalent bonding. Our IR photodissociation spectroscopy with a tunable (3050-3800 cm-1, N-H/O-H stretch region) OPO laser and ESI/FTMS indicates unusually strong H-bonding and structural commonality for gaseous protein ions.
There are now >600,000 different electron ionization mass spectra in our available database. With our Probability Based Matching system, matching an unknown mass spectrum against this database requires <1 s. |
Selected Publications: |
Zabrouskov, V.; Han, X.; Welker, E.; Zhai, H.; Lin, C.: van Wijk, K. J.; Scheraga, H. A.; McLafferty, F. W. Stepwise Deamidation of Ribonuclease A at Five Sites Determined by Top Down Mass Spectrometry (“Hot Article”), Biochemistry, 2006, 45, 987-992.
Chatterjee, A.; Han, X.; McLafferty, F. W.; Begley, T. P. Biosynthesis of Thiamin-Thiazole: Determination of the Regiochemistry of the S/O Acyl Shift by Using 1,4-Dideoxy-D-xylulose-5-phosphate, Angew. Chem., Int. Ed., 2006, 45, 3507-3510.
Han, X.; Jin, M.; Breuker, K.; McLafferty, F. W. Extending Top-Down Mass Spectrometry to Proteins with Masses >200 kDa, Science, 2006, 314, 109-112.
Godert, A. M.; Jin, M.; McLafferty, F. W.; Begley, T. P. An Interesting Twist on Sulfur Transfer in the Biosynthesis of the Thioquinolobactin Siderophore, J. Bacteriol., 2007, 189, 2941-2944. |
