Enzymology at the Membrane Interface: Intramembrane Proteases

Michael H. Gelb studied chemistry and biochemistry as an undergraduate at the University of California at Davis. His Ph.D. studies with Stephen G. Sligar at Yale University led to a better understanding of the catalytic mechanism of cytochrome P450. As an American Cancer Society Postdoctoral Fellow in the laboratory of the late Robert H. Abeles at Brandeis University, Gelb studied a variety of mechanism-based inactivators of serine proteases and developed fluorinated ketones as tight-binding inhibitors of several classes of proteases. In 1985 Gelb became a faculty member in the Departments of Chemistry and Biochemistry at the University of Washington. Major breakthroughs in the group include the development of methods to properly analyze the action of enzymes on membrane surfaces, the discovery of protein prenylation (farnesylation and geranylgeranylation) in mammalian cells (together with John A. Glomset), the development of Isotope-Coded Affinity Tags (ICAT reagents) for proteomic applications (together with Ruedi Aebersold), and the development of newborn screening for lysosomal storage diseases by mass spectrometry.

1. Biochemical Characterization of Function and Structure of RseP, an Escherichia Coli S2P Protease Y. Hizukuri, K. Akiyama and Y. Akiyama 2. Signal Peptidase Enzymology and Substrate Specificity Profiling R.E. Dalbey, D. Pei and Ö.D. Ekici 3. Screening and Characterization Strategies for Nanobodies Targeting Membrane Proteins S. Veugelen, M. Dewilde, B.D. Strooper and L. Chávez-Gutiérrez 4. Probing the Activity of Eukaryotic Rhomboid Proteases in Vitro B. Cordier and M.K. Lemberg 5. Expression, Purification, and Enzymatic Characterization of Intramembrane Proteases R. Zhou, Y. Shi and G. Yang 6. Analyzing Amyloid-ß Peptide Modulation Profiles and Binding Sites of ?-Secretase Modulators J. Trambauer, A. Fukumori, B. Kretner and H. Steiner 7. Probing the Structure and Function Relationships of Presenilin by Substituted-Cysteine Accessibility Method T. Tomita 8. A New Method to Determine the Transmembrane Conformation of Substrates in Intramembrane Proteolysis by Deep-UV Resonance Raman Spectroscopy J.W. Cooley, A. Abdine, M. Brown, J. Chavez, B. Lada, R.D. JiJi and I. Ubarretxena-Belandia 9. An Inducible Reconstitution System for the Real-Time Kinetic Analysis of Protease Activity and Inhibition Inside the Membrane R.P. Baker and S. Urban 10. Production of Recombinant Rhomboid Proteases E. Arutyunova, R. Panigrahi, K. Strisovsky and M.J. Lemieux 11. Mechanism and Inhibition of Rhomboid Proteases K. Strisovsky 12. Enzymatic Assays for Studying Intramembrane Proteolysis D.M. Bolduc, D.J. Selkoe and M.S. Wolfe 13. Methods for S¬tructural and Functional Analyses of Intramembrane Prenyltransferases in the UbiA Super Family Y. Yang, N. Ke, S. Liu and W. Li 14. Functional Study of the Vitamin K Cycle Enzymes in Live Cells J.-K. Tie and D.W. Stafford 15. Activity Assays for Rhomboid Proteases E. Arutyunova, K. Strisovsky and J. Lemieux